Microvascular abnormalities in Sj?gren's syndrome: nailfold capillaroscopy.

OBJECTIVE: To describe microvascular abnormalities by nailfold capillaroscopy in patients with primary Sj?gren's syndrome (SS) with or without Raynaud's phenomenon (RP) and those with anticentromere antibodies (ACA). METHODS: Forty patients with SS (14 without RP, 16 with RP, 10 with ACA), 20 patients with scleroderma (SSc) (10 with limited and 10 with diffuse disease) (disease control group) and 40 healthy controls (control group) were evaluated by nailfold capillaroscopy. RESULTS: Capillaroscopic abnormalities in SS ranged from non-specific findings (crossed capillaries) to more specific findings (confluent haemorrhages and pericapillary haemorrhages) or scleroderma-type findings. SS patients with RP presented capillary abnormalities in higher frequency than patients without RP. The majority of SS patients with ACA (80%) presented scleroderma-type findings. CONCLUSION: Nailfold capillaroscopy can be used as a simple non-invasive method to evaluate the microvascular abnormalities in SS patients, especially in those with RP and those with ACA.     

Intraoperative hemofiltration in adults: prevention of hypercirculatory syndrome?

Hypercirculatory syndrome (HCS) after cardiac surgery may be a sequela of extracorporeal circulation due to hemodilution and release of inflammatory mediators. The aim of this study was to investigate the influence of intraoperative hemofiltration (HF) on the incidence of HCS. A prospective cohort study of 80 patients scheduled for elective coronary bypass was performed. The patients were randomized to two groups: in the conventional (CONV) group 40 patients were treated conventionally and in the HF group 40 patients underwent intraoperative HF. There was no perioperative mortality. The incidence of HCS was comparable in both groups (32% in CONV group versus 40% in HF group; n.s.). Mean cardiac output was higher and systemic vascular resistance lower in CONV group patients than in HF group patients, however these differences did not reach statistical significance. According to this data intraoperative HF does not prevent postoperative HCS induced by cardiopulmonary bypass. Further studies are required to identify the etiology of HCS, and to prevent it occurring after open-heart surgery.     

Cardiovascular risk in the metabolic syndrome: Fact or fiction?

In population-based studies, a cluster of cardiovascular risk factors comprising the metabolic syndrome (MetS) has been documented as predictive of cardiovascular disease events and type 2 diabetes. Currently, there are several proposed definitions of the MetS, although data support some advantages of using the 2005 National Cholesterol Education Program Adult Treatment Panel III definition, which is considered superior to most others, including the one from the 2005 International Diabetes Federation study. One controversial issue is that some of the conventional cardiovascular risk factors included in the MetS cluster appear to be equally predictive of cardiovascular outcomes as the syndrome itself (eg, the influence of smoking habits). Further observational and intervention studies are needed to explore this issue and target the core problem of the syndrome, which is proposed to be insulin resistance. Useful therapies for the metabolic syndrome include lifestyle modification and drugs that lower conventional cardiovascular risk factors, such as metformin, the "glitazones," and evidence-based drugs.     

RAAS Inhibitors in the Cardiovascular Continuum: What is Still Missing?

Recently, clinical trials evaluating cardiovascular outcomes with antihypertensive drugs that target the renin-angiotensin-aldosterone system have been dramatically increasing in size. The CONSENSUS trial in 1987 enrolled 253 patients, while Val-HeFT in 1999 enrolled 5,010 patients; indeed, the Val-HeFT subgroup of patients not receiving angiotensin-converting enzyme inhibitors was bigger than the whole CONSENSUS trial even though the 366 patients were only 7% of the total trial population. More recent and ongoing cardiovascular trials have even greater patient numbers with 14,703 patients enrolled in VALIANT, 15,314 in VALUE, 23,400 in ONTARGET and 33,357 in ALLHAT. Part of the reason is that in modern trials, patients in the control group are already receiving optimal therapy. Therefore, in order to be adequately powered to detect any benefit of new drugs, trials must recruit thousands of patients. This expanding trend cannot continue forever because of time and economic constraints and as a result, trials are shifting their design to include composite and surrogate endpoints. In addition, more predefined substudies are being carried out to analyze possible benefits in specific patient populations such as those with type 2 diabetes or renal impairment. Modern trials are also placing more emphasis on protection as a long-term strategy to control cardiovascular risks. Examples of these points, particularly regarding the size of modern cardiovascular trials to have the power to show protective effects, are illustrated by Val-HeFT, LIFE, ELITE II, VALIANT, VALUE, CHARM and NAVIGATOR.     

What is new in Brugada syndrome?

The Brugada syndrome (BrS) and the long QT syndrome are the most frequently diagnosed genetically-conditioned arrhythmogenic syndromes. It is a primary disorder of electric cardiac activity which is demonstrated by elevation of the ST segment in the right precordial leads connected to an increased risk of sudden death in patients without a structural damage of the heart. In this article, an overview of genetic heterogeneity, pathophysiology, ECG diagnostics and therapy possibilities are discussed, including the innovations of the recent years. A brief case report of a patient presenting with syncope and ST segment elevation is described.     

What is new in the Marfan syndrome?

The Marfan syndrome is an autosomal dominant disorder of connective tissue, caused by mutations in the FBN1 gene on chromosome 15. More than 500 mutations have been identified and almost all are unique to an affected individual or family. Genotype--phenotype correlations in the Marfan syndrome have been complicated by the large number of unique mutations reported, as well as by clinical heterogeneity among individuals with the same mutation. A relatively unknown cardiovascular manifestation of Marfan syndrome is dilatation of the main pulmonary artery. Of 50 patients with Marfan syndrome, MR imaging showed in 74% patients an enlarged pulmonary artery root above the upper limit of normal. Aortic elasticity determined by measurement of local distensibility and flow wave velocity with MR imaging is decreased in non-operated patients with Marfan syndrome. Aortic distensibility of the thoracic descending aorta appeared to be the strongest predictor for descending aortic complications. Over the past 30 years improvement of diagnostic modalities and aggressive medical and surgical therapy, have resulted in considerable improvement of life expectancy of patients with Marfan syndrome. Further studies are needed to investigate the role of modulating genes and genotype--phenotype correlations. Long-term follow-up studies may reveal the prognostic significance of aortic elasticity and may identify patients at risk of aortic complications.     

Cardiovascular primary prevention: how high should we set the bar?

Recent trials in cardiovascular medicine have contradicted current practice, and, accordingly, are medical reversals. Extended-release niacin and fenofibrate have failed to provide mortality benefit when added to statin therapy, though both drugs have been used for this purpose for years. Cardiovascular primary prevention is no small matter. Annual spending on statins exceeded $19 billion in 2005, ezetimibe cost over $5 billion in 2007, and fenofibrate costs passed $1 billion in 2009. Given the tremendous price of these medications, and recent trials that have undermined years of practice, we propose that the bar for cardiovascular primary prevention has been raised. Large studies must show improvements in overall mortality before novel agents are recommended and used. The implications of this proposal are considered.     

Sleep and circadian abnormalities in patients with cirrhosis: features of delayed sleep phase syndrome?

Sleep disturbances are common in patients with cirrhosis but their origins are unknown. The aim of this study was to investigate possible involvement of the circadian system. Sleep was monitored for two weeks, in the home environment, using sleep diaries and actigraphy, in 35 patients with cirrhosis (21 men; mean age [±1SD] 58 ± 10 yr) and 12 matched healthy controls (eight men; mean age 56 ± 15 yr); urinary 6-sulphatoxymelatonin (aMT6s), the major metabolite of melatonin, was measured over 56 h, to assess circadian rhythmicity. The patients woke up and got up significantly later than the healthy volunteers and their sleep was significantly more fragmented. Mean 24-hour urinary aMT6s outputs were comparable in the patients and controls (15.5±13.1 vs. 20.3±13.8 μg/24 h) but were significantly lower in the decompensated patients (9.8 ± 11.3 vs. 17.0 ± 13.3 μg/24 h; p = 0.03). Significant 24-hour urinary aMT6s rhythms were observed in 26 (79%) of the 33 patients with complete urine collections; 20 patients had a normally timed (midnight–06:00) urinary aMT6s peak, while it was delayed (≥ 06:00) in the remainder. Significant correlations were observed between abnormalities in the urinary aMT6s profile (delays and/or lack of a 24-hour rhythm) and indices of sleep timing; parallel delays were observed in sleep habits and urinary aMT6s peaks. The association between delayed circadian rhythms and delayed sleep habits observed in approximately one-third of the patients with cirrhosis is reminiscent of ‘delayed sleep phase syndrome’; this condition is managed by attempting to resynchronise the circadian clock by exposure to bright light shortly after morning awakening.