Wild-Type Transthyretin Amyloid Cardiomyopathy: The Gordian-Knot of Novel Therapeutic Regimens.

Wild-type TTR amyloidosis (wtATTR) represents a disease difficult to diagnose with poor prognosis. Increased clinical suspicion is key, allowing for timely diagnosis. Until recently, only off-label therapies were available but recent introduction of disease specific therapy has shown potential to alter the natural history of the disease. Tafamidis, the only currently approved drug for the therapy of wtATTR, provided significantly better survival and quality of life. However, not all subgroups of patients derived equal benefit. This, along with the increased cost of treatment raised question on whether treatment should be invariably administered through the wtATTR population. This review aims to summarize current evidence on the natural history and staging systems for wtATTR, as well as available treatment options. Special consideration is given to the selection process of patients who would be expected to gain maximum benefit from tafamidis treatment, based on an ethical and cost-effective point of view.

Hepatopulmonary syndrome is associated with the presence of hepatocellular carcinoma in patients with decompensated cirrhosis.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a relatively common complication in patients with decompensated cirrhosis. Our aim was to evaluate the prevalence of HPS, its clinical impact, and the possible association between HPS and characteristics of patients with decompensated cirrhosis. METHODS: Patients with stable decompensated cirrhosis admitted to our department and assessed for HPS were included. For each patient, several clinical, laboratory and echocardiographic parameters as well as renal function were recorded. The severity of liver disease was evaluated according to the Model for End-stage Liver Disease and Child-Pugh scores, and renal function was assessed using 51chromium complexed with ethylene diamine tetracetic acid. In addition, the short synacthen test was performed in each patient to evaluate the adrenal function. RESULTS: Sixty-three patients were enrolled, 26 (41.3%) of whom diagnosed with HPS. In multivariate analysis, the presence of hepatocellular carcinoma [odds ratio (OR) 8.1, 95% confidence interval (CI) 5.3-27.9, P=0.045] and salivary cortisol at T60 (60 min after the intravenous injection of 250 µg corticotropin) (OR 0.88, 95%CI 0.71-0.98, P=0.045) were the factors independently associated with HPS. T60 salivary cortisol had relatively good discriminative ability for the presence of HPS (area under the curve=0.73). The presence of HPS was not associated with the outcome (P=0.22). CONCLUSION: In our cohort of patients with decompensated cirrhosis, the presence of hepatocellular carcinoma and T60 salivary cortisol were the only factors independently associated with HPS.

Association between plasma homocysteine levels and coronary artery disease: a population-based study in northern Greece.

OBJECTIVE: Elevated plasma total homocysteine (tHcy) levels constitute a risk factor for coronary artery disease (CAD). We prospectively examined the association of fasting tHcy levels in patients in Northern Greece who had established CAD. PATIENTS AND METHODS: Plasma fasting tHcy levels were measured in 42 patients with angiographically documented CAD and compared to 42 age-, sex-, BMI- and smoking habit-matched control subjects. We also determined the plasma vitamin B(12), folic acid and lipoprotein levels in all patients and controls. Conventional risk factors for CAD were also estimated. RESULTS: In a univariate analysis, tHcy (micromol/l) levels were higher in patients compared to controls almost reaching statistical significance (13 (7-41) vs 11.3 (4-39); p= 0.07). Multivariate analysis of conventional risk factors showed that tHcy levels were not an independent risk factor for CAD. However, tHcy levels were significantly higher in patients with a previous history of myocardial infarction compared to patients without such a history and to controls (15 (8.8-29) vs 11.7 (7-41); p = 0.007 and 15 (8.8-29) vs 11.3 (4-39); p = 0.002, respectively). Hyperhomocysteinaemia (> 15 micromol/l) was detected in 35.7% of patients and 11.9% of controls (p < 0.05). CONCLUSIONS: In Northern Greece, plasma tHcy levels may not be an independent risk factor for CAD in patients with angiographically documented CAD. However, patients with CAD have a trend towards higher tHcy levels. Additionally, plasma tHcy levels may be associated with the development of myocardial infarction.

Preconditioning reduces QTc value in patients with first non-ST-segment elevation myocardial infarction (NSTEMI).

BACKGROUND: Preinfarction angina (PA) consists a strong clinical correlate to ischemic preconditioning (PC) and seems to occur in a bimodal time course. The aim of the study is to evaluate the impact of both forms of PC on QTc value representing myocardial electric stability, in patients with a first NSTEMI. METHODS: Forty-eight patients, with first NSTEMI and poor or no collateral development were enrolled in the study. QTc at admission and discharge were recorded. All patients had comparable admission QTc values and were divided into three groups according to the absence or presence and exact timing of preinfarction angina. The first group consisted of 20 patients who did not report PA (PA-, representing no PC effect); the second group of 12 patients with reported PA within 12 hours prior to admission (12h PA+, representing the classic form of PC); and the third group of 16 patients reporting PA within 12 to 48 hours prior to admission (48-hour PA+, representing the delayed form of PC). The primary outcome was determined as the effect of PA on QTc value at discharge. RESULTS: Discharge QTc values were significantly reduced in both (PA+) groups compared to (PA-) group (412 +/- 50 vs. 455 +/- 53 ms, p = 0.015 and 417 +/- 29 vs. 455 +/- 53 ms, P = 0.033, respectively). Both groups of (PA+) patients compared to (PA-) patients suffered no arrhythmic events during their hospitalization (0/12 vs. 6/20, P = 0.04 and 0/16 vs. 6/20, P = 0.02). CONCLUSIONS: Both forms of preconditioning, similarly and significantly reduce QTc value at discharge in patients experiencing a first NSTEMI, suggesting possible protection from future arrhythmic events.