Does statin therapy impact the proximal aortopathy in aortic valve disease?

BACKGROUND: Studies have demonstrated that statin therapy decreases the growth rate of abdominal aneurysms. However, the effect of statin therapy on the proximal aortic disease has not been sufficiently elucidated. AIM: We aimed to analyse the association between statin treatment and the severity of proximal aortopathy in patients with aortic valve disease. DESIGN: Cross-sectional study. METHODS: We prospectively identified 458 patients who were referred for aortic valve surgery from 2008 to 2014. Pre-operative measurement of the proximal aorta was performed by TEE, CT or MRT scan. Data of dyslipidemia treatment was obtained by questionnaire. RESULTS: The mean ascending aortic diameter in the whole study population was comparable in patients with vs. without statin therapy (i.e. 42.7 mm vs. 43.6 mm, P = 0.46). Logistic regression analysis showed no significant association between statin therapy and proximal aortopathy ≥ 40 mm in the whole study group (OR = 0.69, P = 0.10). For the BAV sub-group, HDL (OR = 0.54, P = 0.038) and cholesterol levels (OR = 2.00, P = 0.038) were found significantly associated with the proximal aortic disease. In the BAV cohort, the statin users with target HDL levels presented a significantly smaller proximal aortic diameter (40.1 mm vs. 46 mm, P = 0.02). CONCLUSION: Pre-operative statin therapy demonstrated no significant association with the expression of proximal aortopathy. However, more than 40% of the statin users presented uncontrolled lipid levels at the time of the study. In the BAV sub-group, the statins users with target HDL levels showed a significantly smaller ascending aorta diameter. Target HDL and cholesterol levels were strongly associated with proximal aortic dilation in BAV patients.

Increased risk of late aortic events after isolated aortic valve replacement in patients with bicuspid aortic valve insufficiency versus stenosis.

AIM: Bicuspid aortic valve (BAV) is a very heterogeneous disorder and risk of aortic events in BAV may be influenced by phenotype of the disease. Correlation has been proposed between aortic dilatation patterns and functional status of the BAV (i.e., stenosis versus insufficiency). The aim of our study was to evaluate the risk of late aortic events after isolated aortic valve replacement (AVR) in patients with BAV stenosis versus insufficiency. METHODS: Review of our institutional BAV database identified 442 consecutive BAV patients (mean age 55±12 years, 76% men), who underwent isolated AVR from 1995 through 2005. A subgroup of 376 (85%) patients presented with an isolated/predominant BAV stenosis (Group I), whereas 66 (15%) patients had an isolated BAV insufficiency (Group II). Follow-up information (a total of 3864 patient-years) was 100% complete. Mean follow-up period was 9.4±3.9 years. Adverse aortic events were defined as the need for proximal aortic surgery or the occurrence of aortic dissection/rupture, or sudden death during follow-up. RESULTS: Actuarial survival rates in Group I and Group II were 86±2% vs. 94±3% at 10 years, and 76±3% vs. 85±6% at 15 years, respectively (P=0.2). Proximal aortic surgery was performed in 6 (1.5%) patients in Group I vs. 2 (3%) patients in Group II. Freedom from proximal aortic re-interventions was 95±3% in Group I vs. 90±8% in Group II at 15 years after AVR (P=0.4). Aortic dissection/rupture occurred in 2 patients in Group II. Freedom from late adverse aortic events was 93±3% in Group I vs. 78±9% in Group II at 15 years postoperatively (P=0.02). CONCLUSION: BAV patients with isolated valve insufficiency are at increased risk of late aortic events, as compared with BAV stenosis patients at 15 years after AVR.

Plasma homocysteine levels & 677C-->T methylenetetrahydrofolate reductase gene polymorphism in patients with coronary artery disease of different severity.

BACKGROUND & OBJECTIVE: Numerous studies have identified hyperhomocysteinemia as an independent risk factor for coronary artery disease (CAD). Furthermore, influences of polymorphysim of methylenetetrahydrofolate reductase (MTHFR) on homocysteine levels are documented. However, the relationship between severity of CAD and polymorphism of MTHFR has not been systematically evaluated. The present study was undertaken to evaluate this relationship in patients undergoing coronary artery bypass surgery. METHODS: Serum homocysteine and MTHFR polymorphism in relation to severity of CAD was examined in 113 male patients, who all underwent coronary artery bypass surgery. The prevalences of 677 C-->T transition of the MTHFR gene were determined in these patients. Two groups were compared according to GENSINI coronary score : mild atherosclerosis (CAD stenosis < 30) and severe atherosclerosis (CAD stenosis > 30). RESULTS: Patients with CAD showed a significantly higher serum concentration of homocysteine than control subjects (P < 0.01). The serum homocysteine level was significantly higher in patients with increased scores than in patients with mild CAD (Gensini score < 30) both with and without the MTHFR polymorphism. INTERPRETATION & CONCLUSION: The findings of our study showed that hyperhomocysteinemia was significantly related to the severity of CAD independent on MTHFR polymorphism.

Surgical therapy of ventricular arrhythmias.

Since the advent of implantable cardioverters/defibrillators (ICD) and percutaneous ablation, surgery for the treatment of ventricular arrhythmia has decreased tremendously. Nevertheless, surgical treatment of ventricular arrhythmias is still required, especially for cases where ICD discharge occurs very frequently or in patients with other indications for surgery. The choice of surgical therapy may range from radiofrequency- or cryoablation of a single focus (identified either intra- operatively or percutaneously) to more extensive surgical procedures such as surgical ventricular reconstruction with endocardial resection or even resection of the right ventricle and the creation of a cavo-pulmonary circulation for malignant arrhythmias and right ventricular failure in patients with arrhythmogenic right ventricular dysplasia. However, the choice of surgical procedure should be made based on the pathomechanism of the arrhythmia. This is important because any incision in the left or right ventricle or percutaneous ablation may also be the cause for ventricular arrhythmia. In this short review we will describe the most common underlying substrates for ventricular arrhythmia, indications for surgery, the techniques used for treatment and the results achieved. We will conclude that for most cases of patients with ventricular arrhythmia undergoing surgery, ischemia and the presence of a scar after myocardial infarction is the underlying cause and revascularization plus surgical ventricular reconstruction with endocardial resection may be the best treatment option.

Genetic Polymorphism of Methylenetetrahydrofolate Reductase (MTHFR) and Coronary Artery Disease.

A high plasma homocysteine concentration is a risk factor for atherosclerotic disease and venous thrombosis. Homocysteine levels are influenced by folic acid, vitamin B 6 and vitamin B 12, as well as by hereditary factors. A common genetic variant of the methylenetetrahydrofolate reductase (MTHFR) gene CC 677 T) is associated with thermolability of the MTHFR enzyme and elevated plasma homocysteine concentration, especially in those with low folic acid concentration. The prevalence of point mutation (nucleotide 677 C --> T) in MTHFR was measured in patients with coronary artery disease (CAD) who all underwent coronary artery bypass surgery (62 cases; age 64.0 +/- 9.5 years), and was compared with, age-matched control subjects. In patients with coronary artery disease (CAD), we investigated the prevalence of point mutation (nucleotide 677 C --> T) in MTHFR in comparison with control subjects. Heterozygous (C/T) prevalence for the 677 C --> T mutation in the MTHFR was higher in patients with CAD than in control subjects (P < 0.05). The prevalence of homozygosity (C/C) for wild-type MTHFR was lower in patients with CAD in comparison with control subjects (P < 0.05).

Experimental effects of cardiomyoplasty on stressed normal left ventricle in sheep.

OBJECTIVE: Several basic mechanisms of cardiomyoplasty were discussed in the last years, but the definite underlying mechanism is still unknown. The aim of the present study was to determine the effects of cardiomyoplasty on pressure volume loops of the non-failed left ventricle under different myocardial working conditions. METHODS: We performed cardiomyoplasty in eight female sheep after conditioning of the left latissimus dorsi muscles. To simulate different stress conditions we used myocardial stimulation up to 150/min and an increased afterload up to 140 mm Hg. The changes of left ventricular pressure and volume, aortal pressure and aortal flow were registered and analyzed. RESULTS: We found a significant decrease direct cardiomyoplasty effects during simulated stress conditions with increased heart rate up to 150/min and an increased afterload up to 140 mm Hg. We have seen direct effects in the non-failing hearts at rest only. CONCLUSIONS: These findings do not favor the concept of direct cardiomyoplasty-induced improvement of cardiac function under stress conditions. It seems that the conditioned and transformed skeletal muscle already under normal perfusion conditions in normal hearts is not able to generate enough force for an effective contraction under stress conditions. We conclude that the mechanism of cardiomyoplasty can not be explained by a direct effect of muscular support alone but results also from recovery of failed myocardium.