João Silva Marques

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.

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.

The vulnerable plaque: Current concepts and future perspectives on coronary morphology, composition and wall stress imaging

Cardiovascular imaging plays an important role in the identification and characterization of the vulnerable plaque. A major goal is the ability to identify individuals at risk of plaque rupture and developing an acute coronary syndrome. Early recognition of rupture-prone atherosclerotic plaques may lead to the development of pharmacologic and interventional strategies to reduce acute coronary events. We review state-of-the-art cardiovascular imaging for identification of the vulnerable plaque. There is ample evidence of a close relationship between plaque morphology and patient outcome, but molecular imaging can add significant information on tissue characterization, inflammation and subclinical thrombosis. Additionally, identifying arterial wall exposed to high shear stress may further identify rupture-prone arterial segments. These new modalities may help reduce the individual, social and economic burden of cardiovascular disease.

Hypertrophic cardiomyopathy or non-compaction? How the first impression can be wrong

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare disease, resulting from the interruption of myocardial compaction during embryonic growth. Clinical signs are variable, ranging from lack of symptoms to severe manifestations, as heart failure, thromboembolic events, arrhythmias or sudden cardiac death. LVNC is not uncommonly misdiagnosed and, in this regard, multimodality cardiovascular imaging may add important diagnostic information. We report the case of a 46-year-old African black man with no previous significant cardiovascular history, who presented to the emergency department with chest pain, increased cardiac troponin I (31.2 ng/dL) and the ECG showed T wave inversion in lateral and inferior leads, being admitted for non-ST elevation acute myocardial infarction (AMI). Two-dimensional echocardiography performed in the emergency setting showed wall motion abnormalities with posterior akinesia and lateral wall hypokinesia. Non-obstructive assymetric septal and apical hypertrophy was noted in 4-chamber (Fig. 1-A) and parasternal long axis (Fig. 1-B) views. An early invasive strategy was pursued and coronary angiography showed normal coronary arteries. Cardiac magnetic resonance (CMR) was subsequently performed with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Surprisingly no left ventricular hypertrophy was demonstrated, but a hypertrabeculated pattern with deep recesses in the left ventricular apical wall, meeting LVNC criteria (ratio between the

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

Thrombosed aneurysm of the left sinus of valsalva presenting as an intramyocardial mass.

Aneurysms of the sinuses of Valsalva are uncommon in clinical practice. Most are congenital, but secondary causes are also recognized. Congenital aneurysms of the left sinus of Valsalva are particularly rare. The authors report a fatal case in which a nonruptured aneurysm of the left sinus of Valsalva dissected into the interventricular septum and presented as heart failure. The concurrent presence of dilated cardiomyopathy and the mechanisms that may have led to it are discussed on the basis of the anatomic and histologic features found at autopsy.

Clinical use of multimodality imaging in the assessment of dilated cardiomyopathy

Learning objectives: =To understand the use of cardiovascular imaging for diagnosis, evaluation of prognosis and for supporting treatment decisions and monitoring therapy in patients with dilated cardiomyopathy by providing morphologic, functional and etiologic information, including refined assessment of ventricular function. =To provide to the clinical cardiologist the information on what to expect from each imaging modality and how to work together with the cardiovascular imaging expert to fully explore the potential of complementary imaging techniques. = To provide a look into the future role of new imaging modalities such as molecular imaging.

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.

Nova mutação na síndroma de QT Longo em doente com diagnóstico prévio de epilepsia

Congenital long QT syndrome (LQTS) can present as syncope or seizures, secondary to polymorphic ventricular tachycardia, mimicking a primary seizure disorder. In patients treated with an implantable cardioverter-defibrillator (ICD), the recurrence of arrhythmias with subsequent frequent therapeutic shocks may cause adverse reactions, which can be psychogenic. We report the case of a 22-year-old woman with syncope and seizures who was diagnosed in childhood as epileptic and in whom LQTS was diagnosed only in adulthood. Beta-blocker therapy failed and an ICD was implanted. However, as arrhythmias persisted, left cardiac sympathetic denervation was performed. After surgery, three-month follow-up showed a significant reduction in arrhythmias. The genetic study identified a heterozygous mutation, c.1817 C>T p.S606F, on the KCNH2 gene that has not previously been reported in the literature. We also report the rare occurrence of an electrical storm in the course of H1N1 infection. This case illustrates the difficulties in the diagnosis and treatment of LQTS. The possibility of a common genetic basis for arrhythmic diseases and epilepsy is discussed.

Ecocardiografía tridimensional en la cardiopatía carcinoide

A 67-year-old man had presented 7 months earlier with complaints of flushing, diarrhea and tiredness. Etiologic investigation diagnosed metastatic midgut neuroendocrine carcinoid tumor for which he had trans-arterial embolization and started monthly sandostatin. In follow-up, he developed progressive exertional dyspnea and was referred for carcinoid heart screen. On physical examination there were systolic and early diastolic right-sided murmurs, increased jugular venous pressure with prominent v wave and pitting peripheral edema. Bidimensional transthoracic echocardiography showed hypomobile fibrotic tricuspid leaflets that resulted in incomplete coaptation and severe regurgitation. The pulmonary valve was not clearly visualized but there was evidence of moderate regurgitation and mild stenosis. Three-dimensional (3D) echocardiography using volume-rendered imaging provided global simultaneous assessment of the three tricuspid leaflets, which were thickened,