Haralampos Karvounis

Evidence of Left Ventricular Dysfunction in Asymptomatic Elderly Patients with Non-insulin-dependent Diabetes Mellitus

Diabetic cardiomyopathy is a distinct entity in diabetic patients with congestive heart failure, who have no angiographic evidence of significant coronary artery stenosis. The aim of this study was to evaluate left ventricular (LV) function in 24 elderly patients (mean age 67 ±2 years) with type 2 diabetes, who were asymptomatic and had no history of hypertension, or coronary or valvular heart disease. LV systolic indices (ejection fraction [EF] and fractional shortening [FS]), diastolic indices (E wave, A wave, E/A ratio, isovolumic relaxation time [IVRT] and deceleration time [DT]) and the myocardial performance index (MPI) were evaluated with echocardiography. Compared to controls (24 age- and gender-matched normal subjects), the E wave was reduced (0.60 ±0.10 m/sec vs 0.72 ±0.08 m/sec, p<0.05), the A wave was increased (0.77 ±0.07 m/sec vs 0.68 ±0.06 m/sec, p<0.05), the E/A ratio was decreased (0.78 ±0.20 vs 1.06 ±0.18, p<0.001) and both IVRT and DT were prolonged (0.115 ±0.01 sec vs 0.09 ±0.01 sec, p<0.001 and 0.240 ±0.04 sec vs 0.180 ±0.03 sec, p<0.001, respectively). The MPI was significantly increased (0.640 ±0.170 vs 0.368 ±0.098, p<0.001). LV diastolic function and the MPI are markedly impaired in asymptomatic elderly patients with type 2 diabetes.

Evidence of ischemic preconditioning in patients experiencing first non-ST-segment elevation myocardial infarction (NSTEMI)

BACKGROUND Several studies have demonstrated the protective effects of preinfarction angina in Q wave myocardial infarction, implicating the role of ischemic preconditioning but this role remains uncertain in patients with a NSTEMI. Subendocardial viability in NSTEMI patients, is thought to be less dependent on collateral circulation and thus more likely to be protected by other mechanisms such as preconditioning. METHODS We have studied prospectively 40 patients with first NSTEMI and with angiographically proven poor or no collateral development and compared two groups; those with versus those without preinfarction angina. All in-hospital events, such as recurrent angina, congestive heart failure, arrhythmias and reinfarction were recorded. Serum markers of myocardial necrosis (CPK, CPK-MB, AST) and discharge QTc values were estimated. RESULTS Preconditioned patients suffered less recurrent angina (18 vs. 55% P=0.014), congestive heart failure (0 vs. 22%, P=0.02), arrhythmic events (0 vs. 27%, P=0.008) and had significant smaller values of mean peak CPK (381 +/- 152 vs. 859 +/- 496 I.U./l, P=0.0008), mean peak CPK-MB (45.5 +/- 24.6 vs. 105.2 +/- 87 I.U./l, P=0.01), mean peak AST (59.8 +/- 23.1 vs. 112.4 +/- 64.3 I.U./l, P=0.003) and QTc value at discharge (0.42 +/- 0.03 vs. 0.46 +/- 0.05 s, P=0.005) than patients without preconditioning. Multiple logistic regression analysis confirmed that the absence of preinfarction angina (relative risk 9.10, 95% CI 2.08-40.00, P=0.003) was a significant predictor of in-hospital complications. CONCLUSIONS Preinfarction angina constitutes a strong clinical correlate to ischemic preconditioning in patients with first NSTEMI, offering serious protection, by improving in-hospital outcome and reducing infarct size.

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

SUMMARY 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 B12, folic acid and lipoprotein levels in all patients and controls. Conventional risk factors for CAD were also estimated. Results: In a univariate analysis, tHcy (jumol/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|imol/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.

Patients with intracranial bleeding and atrial fibrillation treated with left atrial appendage occlusion: Results from the Amplatzer Cardiac Plug registry.

BACKGROUND In patients with non-valvular atrial fibrillation (NVAF), intracranial bleeding (ICB) constitutes a very challenging situation in which the rate of both ischemic and hemorrhagic events is increased. In these patients, left atrial appendage occlusion (LAAO) might represent a very valid alternative. OBJECTIVES To investigate the procedural safety and long-term outcome of patients undergoing LAAO therapy due to previous ICB. METHODS Data from the Amplatzer Cardiac Plug multicenter registry on 1047 consecutive patients were analyzed. Patients with previous ICB as indication for LAAO were compared to patients with other indications. RESULTS A total of 198 patients (18.9%) with previous ICB were identified. The CHA2DS2-VASc score was similar (4.5±1.5 vs. 4.4±1.6, p=0.687) and the HAS-BLED score was higher in patients with previous ICB compared to those without (3.5±1.1 vs. 3.1±1.2, p<0.001). No significant differences in peri-procedural major adverse events were observed (2.5 vs 5.4%, p=0.1). Patients with previous ICB were more frequently on single acetylsalicylic acid therapy after LAAO (42.4% vs. 28.3%; p<0.001). With an average follow-up of 1.3years, the observed annual stroke/TIA rate (procedure and follow-up) for patients with previous ICB was 1.4% (75% relative risk reduction). The observed annual major bleeding rate (procedure and follow-up) for patients with previous ICB was 0.7% (89% relative risk reduction). CONCLUSIONS In patients with NVAF and previous ICB, LAAO seemed to be a safe procedure and was associated with a significant reduction in stroke/TIA and a remarkably low frequency of major bleeding during follow-up.

Feasibility and Significance of Preclinical Diagnosis in Hypertrophic Cardiomyopathy.

Psoriasis is a common, chronic, autoimmune condition characterized by excessive growth and differentiation of keratinocytes that affects approximately 1% to 3% of the general population in the United States. Mounting evidence has led to an increasing awareness that psoriasis as a disease is more than “skin deep” and that it shares systemic manifestations with other chronic inflammatory diseases such as Crohn’s and diabetes mellitus. Recent studies have not only shown an increased prevalence of cardiovascular risk factors in psoriasis but have also identified psoriasis as an independent risk factor for developing cardiovascular disease. This calls for an approach beyond managing traditional risk factors, which remain the standard guidelines at present.Preclinical diagnosis in hypertrophic cardiomyopathy (HCM) refers to the detection of functional or histopathological abnormalities in subjects who carry any HCM-causing gene mutation, before or even without the development of left ventricular hypertrophy [genotype(+)/phenotype(-)subjects]. The concept that HCM pathology may exist in the absence of left ventricular hypertrophy is quite old but the ability to recognize the presence of early myocardial changes is quite new. Lessons from animal models have shown that in experimental human HCM, myocardial cell mechanical dysfunction precedes histopathological changes, such as myocyte disarray, fibrosis, and hypertrophy. Several clinical reports have demonstrated that the majority of HCM genotype(+)/phenotype(-) subjects display myocardial functional or histopathological changes, such as reduced tissue Doppler imaging-derived systolic and diastolic velocities, abnormal electrocardiogram, cardiac magnetic resonance-visualized myocardial crypts, mitral leaflet elongation, and evidence of a fibrotic state, such as increased type I procollagen synthesis, cardiac magnetic resonance-increased myocardial extracellular volume, and late gadolinium myocardial enhancement. All these signs have been proposed as preclinical markers of HCM. At present the separation of such a group of subjects in the early phase of their disease provides the opportunity to test new therapies to prevent the development of fibrosis, hypertrophy, and dysfunction.

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.

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.

Elevated plasma levels of miR-29a are associated with hemolysis in patients with hypertrophic cardiomyopathy

BACKGROUND miR-29a is a small non-coding RNA that is known to repress collagen synthesis. Interestingly, elevated plasma miR-29a was reported to correlate with pronounced myocardial fibrosis in patients with hypertrophic cardiomyopathy. The objective of this study was to elucidate the origin of plasma miR-29a, and evaluate its significance as a biomarker. METHODS miR-29a expression was evaluated in plasma (n=50) and myocardial samples (n=4) from patients with hypertrophic cardiomyopathy using RT-qPCR. RESULTS Although miR-29a was highly expressed in the myocardium, miR-29a plasma levels did not show any correlation with serum troponin I levels (rs=-0.12, p=0.43), and the heart does not release significant amounts of miR-29a into the circulation via exosome secretion. Conversely, miR-29a was present in red blood cells, and plasma levels correlated significantly with markers of hemolysis: lactic dehydrogenase (rs=0.36, p=0.01) and the absorbance of oxyhemoglobin at 414nm (rs=0.39, p=0.006). Furthermore, the association between serum haptoglobin and the maximal blood flow velocity in the left ventricle outflow tract (rs=-0.42, p=0.008) indicated that intravascular hemolysis is a manifestation of the disease. CONCLUSIONS miR-29a is highly expressed in myocardial tissue from patients with hypertrophic cardiomyopathy. In contrast, plasma miR-29a is primarily of nonmyocardial origin and is correlated significantly with the extent of hemolysis observed in these patients.