Periostin is overexpressed, correlated with fibrosis and differs among grades of cardiomyocyte hypertrophy in myectomy tissue of patients with hypertrophic cardiomyopathy.

Periostin, a secreted matricellular protein, has been implicated in cardiac extracellular matrix remodeling and fibrosis. Evidence suggest that periostin stimulates cardiomyocyte hypertrophy. The current study aims to investigate the extent of periostin expression in patients with advanced Hypertrophic Cardiomyopathy (HCM) and its correlation with fibrosis and hallmark histopathological features of the disease. Interventricular septal tissue from thirty-nine HCM patients who underwent myectomy and five controls who died from non-cardiac causes was obtained. Staining with Masson's Trichrome and immunohistochemistry were used to localize fibrosis and periostin respectively. The extent of fibrosis and the expression of periostin were defined as the stained percentage of total tissue area using digital pathology software. Periostin expression was higher in HCM patients compared to controls (p<0.0001), positively correlated with the extent of fibrosis (r = 0.82, p<0.001), positively correlated with maximal interventricular septal thickness (Rho = 0.33, p = 0.04) and negatively correlated with LVEF (r = -0.416, p = 0.009). Periostin was approximately co-localized with fibrosis. Mean periostin expression was lower in patients with mild grade cardiomyocyte hypertrophy compared to those with moderate grade (p = 0.049) and lower in patients with mild grade replacement fibrosis compared to moderate grade (p = 0.036). In conclusion, periostin is overexpressed in advanced HCM, correlated with fibrosis and possibly related to cardiomyocyte hypertrophy.

Routine histopathology of septal myectomy for hypertrophic obstructive cardiomyopathy in a greek cohort.

Hypertrophic cardiomyopathy (HCM) is a diverse inherited disease affecting 1 in 500 individuals irrespective of gender and ethnicity. A fraction of HCM patients will eventually develop drug refractory dynamic obstruction of the left ventricular outflow tract. For such patients, septal myectomy is the procedure of choice to alleviate their symptoms and improve their quality of life. The current histopathological study, the first from the Greek region, aims to examine the hallmark histopathological characteristics of Hypertrophic Obstructive Cardiomyopathy in a population of patients undergoing septal myectomy at a single center over a ten year period. Medical records and histopathology specimens of thirty nine (n=39) patients were evaluated. The sample comprised 22 males (56.4%) and 17 females (43.6%). Mean patient age at myectomy was 53.9±16.7 years, ranging from 12 to 79 years. Maximal IVS thickness on echocardiography was available for 35 patients with a median value of 2.08cm. Peak resting LVOT Pressure Gradient was available for 33 patients with a mean value of 104.88±44.20 mmHg. Central tendency of each histopathological attribute expressed as the median value was: moderate for myocyte hypertrophy, mild for cytoplasmic vacuolization, moderate for subendocardial fibrosis, moderate for interstitial fibrosis, mild for replacement fibrosis, moderate for myofibrillar disarray and mild for capillary stenosis. Myocyte hypertrophy, present in all specimens, was positively correlated with maximal IVS thickness (tau-b=0.43, p=0.002). Replacement fibrosis was positively correlated with the grade of microvascular stenosis (tau-b=0.45, p=0.004). LVEF was negatively correlated with the grade of interstitial fibrosis (tau-b=-0.43, p=0.035) and with the extent of myocardial fiber disarray (tau-b=-0.42, p=0.034). Histopathological attributes were not correlated with patient gender or age thus proving that HCM has a histological phenotype unique to each patient, mainly depending on each specific sarcomeric mutation.

Mitral valve repair: moving towards a personalized ring.

BACKGROUND: Mitral valve repair with the use of an annuloplasty ring is the procedure of choice in patients with significant mitral regurgitation (MR) due to floppy mitral valve (FMV)/mitral valve prolapse (MVP). The mitral annular size, shape and motion may vary substantially among patients and thus, commercially available rings may not be suitable for each individual patient. METHODS: A "personalized ring" (PR) was easily constructed in the operating room using a Dacron sheet and titanium ligating clips to custom fit to each individual mitral annulus shape and size. There were 127 patients with severe MR due to FMV/MVP that underwent mitral valve repair surgery; 58 patients received a PR and 69 patients received a commercial Carpentier-Edwards Physio II ring. The patient records were retrospectively analysed. RESULTS: There were no surgical deaths. In-hospital length-of-stay and blood transfusions were not statistically different between the two groups. Mitral valve area was greater (p < 0.05) in the PR group (3.78 ± 0.22) compared to the Physio II ring group (3.13 ± 0.21). Mitral annular area changed from systole to diastole by 14.35% ± 3.28% in the PR group and did not change in the Physio II ring group (p < 0.05). Systolic anterior motion (SAM) of the mitral valve occurred in 2 patients with the Physio II ring and no patients with the PR. Up to 8 years follow-up, all patients in both groups were alive with NYHA functional class I-II symptoms and mild or less MR. CONCLUSIONS: The PR is suitable for all patients with significant MR due to FMV/MVP who require MV repair. The precise fit of the PR to the mitral annulus better preserves valve area and sphincter function of the mitral annulus, prevents SAM and provides excellent short and long-term results.

Matrix Metalloproteinase Polymorphisms in Patients with Floppy Mitral Valve/Mitral Valve Prolapse (FMV/MVP) and FMV/MVP Syndrome.

BACKGROUND: It has been suggested that collagen abnormalities of the mitral valve are present in patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP). Genetic factors determining collagen synthesis and degradation have not been well defined in these patients. This study was undertaken to determine whether selective polymorphisms of matrix metalloproteinase-2 (MMP2) or transforming growth factor-ß (TGFß), with known or putative effects on collagen turnover, are more frequent in FMV/MVP. METHODS: Single nucleotide polymorphisms (SNPs) in select genes related to collagen turnover, including MMP2 rs2285053, MMP2 rs243865, TGFß1 rs1800469, and TGFß2 rs900, were determined in 98 patients with FMV/MVP who had severe mitral regurgitation and compared to 99 controls. RESULTS: MMP2 rs243865 was the only SNP significantly associated with FMV/MVP as compared to the control (odds ratio 2.07, 95% CI 1.23-3.50, p = 0.006). MMP2 rs228503 was the only SNP significantly associated with the FMV/MVP syndrome as compared to patients with FMV/MVP without the syndrome (odds ratio 2.41, 95% CI 1.08-5.40, p = 0.032). CONCLUSION: The frequency of certain MMP2 polymorphisms is higher in patients with the FMV/MVP syndrome and patients with FMV/MVP without the syndrome. The data suggest that a genetic predisposition that alters collagen turnover may play a role in the pathogenesis and development of FMV/MVP.

Floppy mitral valve/mitral valve prolapse syndrome: Beta-adrenergic receptor polymorphism may contribute to the pathogenesis of symptoms.

BACKGROUND: Certain patients with floppy mitral valve (FMV)/mitral valve prolapse (MVP) may have symptoms that cannot be explained on the severity of mitral valvular regurgitation (MVR) alone; hypersensitivity to adrenergic stimulation has been suggested in this group defined as the FMV/MVP syndrome. METHODS: Ninety-eight patients (75 men, 23 women) with mitral valve surgery for FMV/MVP were studied. Of those 41 (42%) had symptoms consistent with FMV/MVP syndrome [29 men (39%), 12 women (52%)]; median age of symptom onset was 30 years (range 10-63 years) and median duration of symptoms prior to valve surgery was 16 years (range 3-50 years). Ninety-nine individuals (70 men, 29 women) without clinical evidence of any disease were used as controls. Genotyping of ß1 and ß2 adrenergic receptors was performed. RESULTS: ß-Adrenergic receptor genotypes (ß1 and ß2) were similar between control and overall FMV/MVP patients. Subgroup analysis of patients, however, demonstrated that the genotype C/C at position 1165 resulting in 389 Arg/Arg of the ß1 receptor was more frequent in women compared to those without FMV/MVP syndrome and to normal control women (p<0.025). This polymorphism may be related to hypersensitivity to adrenergic stimulation as reported previously in these patients. CONCLUSION: This study shows a large proportion of patients with FMV/MVP, predominantly women, had symptoms consistent with the FMV/MVP syndrome for many years prior to the development of significant MVR, and thus symptoms cannot be attributed to the severity of MVR alone. Further, women with FMV/MVP syndrome, symptoms at least partially may be related to ß1-adrenergic receptor polymorphism, which has been shown previously to be associated with a hyperresponse to adrenergic stimulation.

Surgical septal myectomy for hypertrophic cardiomyopathy in Greece: a single-center initial experience.

INTRODUCTION: Surgical septal myectomy is thought to be the gold standard of treatment for obstructive hypertrophic cardiomyopathy (HCM) with obstruction symptoms refractory to optimal medical therapy. In Europe, during the last 2 decades, myectomy has been set aside, while alcohol septal ablation has been widely promoted. In this paper, we analyze our first experience of surgical septal myectomy in a small cohort of patients with HCM coming from a single tertiary center. METHODS: Thirty-two patients (16 male, 50%) with a mean age of 58.1 ± 14.4 (range 12-79 years) underwent myectomy for HCM symptoms refractory to negative inotropic agents. The technique used for the myectomy was the one introduced by Andrew Morrow. Mean follow-up time after procedure was 16.8 ± 13.3 months with a median of 13 months (range 4-58 months). RESULTS: Post-myectomy, there was a significant improvement in patients' NYHA class (from 3.3 ± 0.46 to 1.38 ± 0.49, p<0.0005), while interventricular septum thickness was reduced from 2.3 ± 0.4 cm to 1.6 ± 0.4 cm (p<0.0005), and peak gradient at the site of obstruction from 94.9 ± 29 to 16.7 ± 7.9 mmHg (p<0.0005). During the follow-up period, only 1 out of 32 patients died, from non-cardiovascular causes, with the overall survival post-myectomy being 97.2% (95%CI: 94.5-99.9%) at 1-year follow up. CONCLUSIONS: Surgical septal myectomy in patients with HCM and drug-refractory symptoms is a safe procedure that greatly improves symptoms and quality of life. Further follow-up of our patients is mandatory in order to determine whether the good survival rate achieved at 1 year will persist.

Prevalence of "distressed" personality in patients with coronary artery disease and its correlation with morbidity after coronary surgery.

INTRODUCTION: The "distressed" (Type-D) personality is an emerging risk factor in cardiovascular diseases and is associated with an increased risk of impaired quality of life, morbidity and mortality. The purpose of this study was to explore the prevalence of Type-D personality among patients with coronary artery disease (CAD) and its association with the development of complications following coronary artery bypass grafting surgery. METHODS: A Greek version of the Type-D Personality Scale-14 (DS14), along with the Hospital Anxiety and Depression Scale (HADS) as well as the Ways of Coping Questionnaire (WCQ), were used. A cohort of 323 patients with CAD was examined. RESULTS: The prevalence of Type-D personality among Greek patients with CAD was found to be 18.24%. Type-D patients showed a higher rate of anxiety and depression compared to non Type-D patients. Type-D was also associated with passive coping and negatively correlated with active coping. Regarding postoperative morbidity, type-D patients were at an increased risk of developing postoperative atrial fibrillation, while no significant differences were found in the development of any other complication. CONCLUSIONS: The impact of Type-D personality on health outcomes should be studied further, both in clinical samples and in the general population.

Minimally invasive transapical aortic valve implantation and simultaneous major pulmonary resection.

We report a 71-year-old male who underwent successful minimally invasive transapical aortic valve implantation to treat severe aortic stenosis, with simultaneous pulmonary resection for the treatment of lung cancer. At five-year follow-up the patient remains free of symptoms (NYHA I) and recurrence.