Novel lipid biomarkers and associated gene polymorphism in young ST-segment elevation myocardial infarction

Background: There is an increasing prevalence of coronary artery disease (CAD) in younger individuals. Lipid biomarkers such as lipoprotein-a (Lp-a), Apo A1, Apo B and Paraoxonase-1 (PON1) serve as important risk predictors for development of CAD. There is little evidence regarding the role of lipid biomarkers and their genetic polymorphisms in young (<50 years) ST-segment elevation myocardial infarction (STEMI) patients. Methods: This study included 110 young (18e50 years) STEMI patients and 110 healthy controls. Serum levels of Apo A1, Apo B, Paraoxonase-1 (PON-1) and Lipoprotein-associated phospholipase A2 (Lp-PLA2) were estimated for both patients as well as controls. Additionally, genetic polymorphisms in the Apo A1 (75G/A) and the PON1 (Q192R) genes were evaluated. Results: Serum levels of apo B (101.31 ± 27.58 vs 75.31 ± 18.77 mg/dl; p < 0.0001), Lp(a) [87.56 ± 74.28 vs 25.81 ± 24.66 mg/dl, p < 0.0001] and Lp-PLA2 [5.97 ± 1.39 vs 3.49 ± 1.27 ng/mL, p < 0.0001] were significantly higher in patients as compared to controls. Serum levels of Apo A1 [44.76 ± 35.65 vs 95.97 ± 29.89; p < 0.0001] and PON1 [2.63 ± 1.5 vs 3.87 ± 1.47 ng/mL, p < 0.0001] were significantly lower in cases as compared with controls. Additionally, patients with genetic polymorphisms in the Apo A1 (75G/A) and the PON1 (Q192R) gene had an increased risk of STEMI. Conclusion: Lipid biomarkers such as Apo A1, Apo B and PON1 and their genetic polymorphism are associated with the susceptibility for STEMI in young individuals.

Matrix metalloproteinases and their gene polymorphism in young ST-segment elevation myocardial infarction

Background: Genetic polymorphism in MMPs are associated with multiple adverse CV events. There is little evidence regarding role of MMPs and their genetic polymorphisms in young (<50 years) STsegment elevation myocardial infarction (STEMI) patients. Methods: This study included 100 young (18e50 years) STEMI patients and 100 healthy controls. Serum levels of MMP-3, MMP-9 and TIMP were estimated for both patients as well as controls. Additionally, genetic polymorphisms in the MMP-9 gene (_x0001_1562 C/T and R279Q) & MMP-3 gene (5A/6A-1612) was evaluated. All these patients were followed up for one year and major adverse cardiac events (MACE) were determined. Results: Serum levels of MMP-3 (128.16 ± 115.81 vs 102.3 ± 57.28 ng/mL; P ¼ 0.04), MMP-9 (469.63 ± 238.4 vs 188.88 ± 94.08 pg/mL; P < 0.0001) and TIMP (5.84 ± 1.93 vs 2.28 ± 1.42 ng/mL; P < 0.0001) were significantly higher in patients as compared to controls. Additionally, patients with genetic polymorphisms in the MMP genes (5A/5A, 6A/6A and the AG genotypes) had an increased risk of STEMI. Patients with MACE had significantly higher levels of MMP-9 (581.73 ± 260.93 vs 438.01 ± 223.38 pg/mL; P ¼ 0.012). A cutoff value of 375.5 pg/mL of MMP-9 was best able to discriminate patients with STEMI and MACE with sensitivity of 77.3% and specificity of 57%. Conclusion: Novel biomarkers such as MMP-3, MMP-9 and TIMP and their genetic polymorphism are associated with the susceptibility for STEMI in young individuals. Higher MMP-9 levels in STEMI patients with MACE suggests its potential role in predicting cardiac remodeling and left ventricular dysfunction

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease

Introduction: The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males. Aim: We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD). Methods: We compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls. Results: The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p ¼0.007 and OR 2.39; p ¼0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p ¼0.047 and OR 2.26; p ¼0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p ¼0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p ¼0.018) were independent predictors of development of PH in females.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20–30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ?30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.

Left atrial function by two-dimensional speckle tracking echocardiography in patients with severe rheumatic mitral stenosis and pulmonary hypertension

We studied left atrial (LA) function in severe rheumatic mitral stenosis (MS) patients using twodimensional speckle tracking echocardiography (STE). Eighty patients with isolated severe MS in sinus rhythm and 40 controls underwent comprehensive echocardiography including STE derived LA strain [reservoir strain (LASr), conduit strain (LAScd) and contractile strain (LASct)]. The mean MVA was 0.93 ± 0.21 cm2 . The mean values of LASr (14.73 ± 8.59%), LAScd (±7.61 ± 4.47%) and LASct (±7.16 ± 5.15%) in patients were significantly lower (p < 0.001) vs. controls 44.11 ± 10.44%, ±32.45 ± 7.63%, -11.85 ± 6.77% respectively and showed decreasing trend with increasing MS severity and higher NYHA class. In conclusion, LA dysfunction is prevalent in severe MS irrespective of NYHA functional class.

Risk factors and angiographic profile of coronary slow flow (CSF) phenomenon in North Indian population: An observational study

Background “Coronary slow flow’’ (CSF) is delayed vessel opacification in the absence of epicardial stenosis. Studies in different ethnic groups have found variable risk factors associated with CSF. Aim of present study was to analyze the risk factors and angiographic profile of CSF in North Indian population, not studied till date. Methods 40 patients with CSF and 40 controls were studied. CSF was determined quantitatively by thrombolysis in myocardial infarction (TIMI) frame count method. Various clinical risk factors (age, sex, body mass Index (BMI), diabetes, hypertension, dyslipidemia, smoking), hematological and biochemical parameters (hematocrit, platelet count, uric acid, homocysteine, fibrinogen, high sensitivity C reactive protein (hsCRP), glycosylated hemoglobin (HbA1c) were assessed. Results Of the 40 patients with CSF, 37 (92.5%) were males. While 20 patients (50%) presented with chronic stable angina, rest 20 (50%) presented with acute coronary syndrome. [15 (37.5%) with unstable angina and 5 (12.5%) with non ST elevation myocardial infarction (NSTEMI)]. Patients with CSF had significantly higher BMI (27.27 ± 2.82 vs. 24.12 ± 2.35, p < 0.001), fibrinogen levels (398.48 ± 120.96 vs. 331.55 ± 162.6, p = 0.04) and smoking (24(60.0%) vs 14(35.0%), p = 0.02). On multivariable regression analysis, only BMI was found to have an independent association with CSF (odds ratio 1.613, 95% confidence interval 1.265–2.057, p < 0.001). Conclusion This is the first study to analyze clinical presentation, angiographic profile and risk factors associated with CSF in North Indian population. In this study, we found only BMI to have an independent association with CSF.

Evaluation of serum 25-hydroxyvitamin D levels in calcific rheumatic mitral stenosis— A cross sectional study

Background and aim of the study Rheumatic mitral stenosis (RMS) is an autoimmune, progressive destructive valve disease occurring as a sequele of streptococcal infection. Epidemiological studies support an association of vitamin D deficiency with initial susceptibility and severity of autoimmune diseases. The aim of the present study was to assess serum level of 25 hydroxyvitamin D in subjects of RMS and assess if any correlation exists with serum levels of vitamin D and severity of disease along with calcification assessed semi-quantitatively by echocardiography by applying Wilkins score. Method Fifty five patients of RMS without any calcification of the valves (Group A) assessed by echocardiography along with fifty five patients of RMS with mild to moderately calcified valves (Group B, Wilkins calcium score 1 or 2) and 55 patients with severely calcified valves (Group C, Wilkins calcium score 3 or 4) were enrolled for the study. All subjects underwent clinical, echocardiographic, and biochemical evaluation. The total Wilkins score, Wilkins calcium score along with serum level of 25 hydroxyvitamin D was evaluated in all the patients. Results The median serum level of 25 hydroxyvitamin D was significantly lower in Group B (20.4 ng/ml, p < 0.001) and group C (11.4 ng/ml, p < 0.001) compared to Group A patients (27.9 ng/ml). Similarly serum level of 25 hydroxyvitamin D in Group C patients were significantly less than Group B patients (p < 0.001). A significant inverse correlation was identified between serum level of 25 hydroxyvitamin D and total Wilkins score (r = −0.65, p < 0.001) as well as Wilkins calcium score (r = −0.69, p < 0.001). But no correlation was identified between 25 hydroxyvitamin D levels and other echocardiographic parameters of RMS. Conclusion Our study showed a significantly lower level of 25 hydroxyvitamin D in subjects of RMS with severely damaged and calcified valves as compared to those with less severely damaged non-calcified valves and it correlated with both Wilkins score and Wilkins calcification score. Thus a link may exist between vitamin D deficiency (an immunomodulator) and severity of autoimmune injury on the valves.

Novel non-surgical method of managing cardiac perforation during percutaneous transvenous mitral commissurotomy.

We describe a new technique of sealing cardiac perforation resulting in cardiac tamponade during transvenous mitral commissurotomy by percutaneous instillation of cyanoacrylate glue at the perforation site, thus avoiding surgery.

Focal extra strength of a stent causing instent hourglass stenosis: an unusual complication.

We report an unusual complication of a 25 mm long stent, which did not expand at all for 1 mm in its proximal segment, while rest of the 24 mm length of the stent got fully expanded. Repeated attempts to expand the extremely focal unexpanded part of the stent at high pressure led to rupture of the stent balloon and its entrapment. We failed to retrieve the balloon using various techniques and the patient had to be sent for coronary artery bypass graft surgery.

Difficult percutaneous transvenous mitral commissurotomy: a new technique for left atrium to left ventricular entry.

Percutaneous transvenous mitral commissurotomy using Inoue balloon is an effective procedure for the management of patients with juvenile mitral stenosis. Inability to cross the mitral valve by the Inoue balloon catheter is one of the important reasons for failure of the procedure. We describe a new technique, facilitating left atrium to left ventricular entry using double loop of Inoue balloon catheter in a child with small left atrium.

Transcatheter closure of coronary artery fistulas.

BACKGROUND: Transcatheter closure of coronary artery fistulas has emerged as a successful alternative to surgery. We describe various techniques and short-term findings in 15 patients who were taken up for transcatheter closure of these fistulas. METHODS AND RESULTS: Fifteen patients (aged 2-55 years; 12 males) with coronary artery fistulas underwent percutaneous transcatheter closure between June 1997 and December 2002. Site of origin of these fistulas were: right coronary artery in 7, left anterior descending coronary artery in 4, left main coronary artery in 2 and left circumflex coronary artery in 2 patients. Drainage site of these fistulas were: right ventricle in 9, right atrium in 4 and pulmonary artery in 2 patients. Out of these 15 fistulas, 14 were congenital and one was iatrogenically produced following inadvertent cutting balloon angioplasty of a septal perforator in a patient with chronic total occlusion of left anterior descending coronary artery. Various occlusion devices used to close these fistulas were: conventional metallic coils in 10, floppy tips of coronary angioplasty guidewires in 2, Amplatzer duct occluder in 1 and Amplatzer septal occluder in 2 patients. One of our patients had a coronary artery fistula draining by two openings into the right atrium, both of which were successfully closed using 2 Amplatzer duct occluders. Check angiogram after the procedure revealed complete occlusion in 13 (86.6%) and small residual flow in 2 patients. Follow-up studies at 3-55 months (mean 18 months) showed complete abolition of shunt in all patients with no evidence of recanalization leading to recurrence of shunt. CONCLUSION: Transcatheter closure of coronary artery fistulas is feasible and safe in the anatomically suitable vessels. Use of floppy tips of coronary angioplasty guidewires reduces the cost of the procedure significantly. which is an important consideration in developing countries like India.

Isolated thrombus producing tricuspid stenosis: an unusual presentation in primary antiphospholipid syndrome.

We report the case of a female patient who presented with signs and symptoms of tricuspid stenosis. Echocardiography revealed a sessile mass on the tricuspid valve. A diagnosis of primary cardiac tumor was made but histopathologic examination revealed the mass to be an organized thrombus. Subsequent serological tests showed elevated titers of anticardiolipin antibodies in the absence of any associated disease. This case highlights an unusual presentation of the primary antiphospholipid syndrome.

Post-stenotic dilatation: challenge in renal ostial stenting--a simple solution.

Stenting is the treatment of choice for treating stenotic renal ostial lesions. During the stenting of an ostial lesion in a renal artery with post-stenotic dilatation, we were faced with the problems of unavailability of a balloon of appropriate length and diameter, and determining the real reference vessel diameter. The problem was solved by a simple technique.

Stenting of a septal perforator for post-myocardial infarction angina.

Occlusion of a septal perforator branch alone, without the involvement of the left anterior descending coronary artery, leading to acute myocardial infarction is unusual. We report a case in which an isolated severely stenotic thrombus-containing first septal artery causing intractable post-myocardial infarction angina was successfully dilated and stented.