Laboratory evaluation of lipid parameters in clinical practice.

Accurate measurement of various lipids- total cholesterol, cholesterol lipoproteins and triglycerides- is important for coronary artery disease (CAD) prevention and management. Over the years many technologies have developed for their accurate measurements and in recent years the assays have been internationally standardised. Most of the guidelines recommend measurement of non fasting levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL cholesterol (non-HDL-C) and triglycerides (TG) for risk estimation and guiding treatment. Measurement of lipid profile in clinics and emergency departments can lead to earlier estimation of CAD risk and rapid initiation of lipid lowering therapy. CAD risk and baseline levels of LDL-C guide intensity of lipid lowering therapies. The LDL-C targets according to CAD risk are detailed in this review. There is an urgent need for standardization of lipid estimation in medical laboratories across the country so that every eligible individual can receive evidence-based lipid lowering interventions.

CSI clinical practice guidelines for dyslipidemia management: Executive summary.

Dyslipidemias are the most important coronary artery disease (CAD) risk factor. Proper management of dyslipidemia is crucial to control the epidemic of premature CAD in India. Cardiological Society of India strived to develop consensus-based guidelines for better lipid management for CAD prevention and treatment. The executive summary provides a bird's eye-view of the 'CSI: Clinical Practice Guidelines for Dyslipidemia Management' published in this issue of the Indian Heart Journal. The summary is focused on the busy clinician and encourages evidence-based management of patients and high-risk individuals. The summary has serialized various aspects of lipid management including epidemiology and categorization of CAD risk. The focus is on management of specific dyslipidemias relevant to India-raised low density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol (non-HDL-C), apolipoproteins, triglycerides and lipoprotein(a). Drug therapies for lipid lowering (statins, non-statin drugs and other pharmaceutical agents) and lifestyle management (dietary interventions, physical activity and yoga) are summarized. Management of dyslipidemias in oft-neglected patient phenotypes-the elderly, young and children, and patients with comorbidities-stroke, peripheral arterial disease, kidney failure, posttransplant, HIV (Human immunodeficiency virus), Covid-19 and familial hypercholesterolemia is also presented. This consensus statement is based on major international guidelines (mainly European) and expert opinion of lipid management leaders from India with focus on the dictum: earlier the better, lower the better, longer the better and together the better. These consensus guidelines cannot replace the individual clinician judgement who remains the sole arbiter in management of the patient.

Case report: management of refractory cardiogenic shock with Impella 5.5 in patients with transcatheter aortic valves.

Background: Impella is a transaortic valvular pump commonly utilized in patients with cardiogenic shock. However, its use with transcatheter aortic valves (TAVI) remains rare. We present two cases where surgical Impella 5.5 was placed across both Sapien 3 Ultra and Evolute Pro+ valves. Case summary: Patient 1: A 74-year-old male with history of ischaemic cardiomyopathy with ejection fraction 20-25% status post-cardiac resynchronization therapy with a defibrillator, severe aortic stenosis (AS) status post-recent Sapien 3 Ultra TAVI presented with cardiogenic shock. Due to persistent unstable haemodynamic status, Impella 5.5 was placed and was utilized as a bridge to left ventricular assist device. Patient 2: A 74-year-old male with a history of alcoholic cirrhosis and AS underwent Evolute Pro+ TAVI at outside facility. The implantation was complicated by left main coronary artery occlusion, leading to cardiogenic shock. Patient required femoral veno-arterial extracorporeal membrane oxygenation (ECMO) support and emergent single vessel coronary bypass of a saphenous venous graft to the left anterior descending artery. Extracorporeal membrane oxygenation was decannulated on Day 20 and Impella 5.5 was placed as a bridge to recovery. In both cases, there were no procedural complications or residual aortic or perivalvular regurgitation. Discussion: Impella 5.5 implanted via the axillary surgical cutdown is safe and feasible approach to manage refractory cardiogenic shock in patients with TAVI including different types of valves, Sapien 3 Ultra, and Evolute Pro+. As it can provide full haemodynamic support, Impella 5.5 can be used as bridge to recovery or durable mechanical support.

Outcomes of surgical Impella placement in acute cardiogenic shock.

Introduction: Although a role for percutaneous Impella devices has been established, there is a paucity of data regarding the utility and outcomes of larger surgically implanted Impella devices. Methods: We conducted a retrospective review of all surgical Impella implants at our institution. All Impella 5.0 and Impella 5.5 devices were included. The primary outcome was survival. Secondary outcomes included hemodynamic and end-organ perfusion as well as commonly encountered surgical complications. Results: From 2012 to 2022, 90 surgical Impella devices were implanted. The median age was 63 [53-70] years, the mean creatinine was 2.07 ± 1.22 mg/dL, and the average lactate level was 3.32 ± 2.90 mmol/L. Prior to implantation, 47 patients (52%) were supported with vasoactive agents, while 43 (48%) were also supported with another device. The most common etiology of shock was acute on chronic heart failure (50, 56%), followed by acute myocardial infarction (22, 24%), and postcardiotomy (17, 19%). Overall, 69 patients (77%) survived to device removal, and 57 (65%) survived to hospital discharge. One-year survival was 54%. Neither etiology of heart failure nor device strategy was associated with 30-day or 1-year survival. On multivariable modeling, the number of vasoactive medications prior to device implantation was strongly associated with 30-day mortality (hazard ratio 1.94 [1.27-2.96], P < 0.01). Surgical Impella placement was associated with a significant decreased need for vasoactive infusions (P < 0.01) and decreased acidosis (P = 0.01). Conclusions: Surgical Impella support for patients in acute cardiogenic shock is associated with lower vasoactive medication use, improved hemodynamics, increased end-organ perfusion, and acceptable morbidity and mortality.

Managing Right Ventricular Failure After Left Ventricular Assist Device Implant at a Destination Therapy Center.

Although left ventricular assist device (LVAD) implant is associated with an increased survival in patients with end-stage heart failure, severe right ventricular failure requiring a right ventricular assist device (RVAD) placement is associated with increased short-term morbidity and mortality. Patients not eligible for transplant have limited options, which may impact decision-making and outcomes at nontransplant centers. We conducted a retrospective review of all LVAD implants at our nontransplant center. Primary stratification was by the need for a postoperative RVAD implant. The primary outcome was survival. The Cox proportional hazards regression modeling was used to further evaluate mortality. From 2017 to 2022, 128 patients underwent a primary LVAD implant and 24 (18.75%) required a perioperative RVAD placement. RVAD implant was associated with increased operative mortality (1.92% vs 33.33%, p <0.01) and decreased 1-year (91.29% vs 60.60%, p <0.01) and 2-year survival (84.05% vs 36.36%, p <0.01). However, in patients who survived their index hospitalization, 1-year (93.00% vs 91.67%, p = 0.78) and 2-year (86.16% vs 55.00%, p = 0.10) mortality were similar. On multivariable analysis, the need for a RVAD was associated with an increased hazard of 1-year (5.60 [1.96 to 16.01], p <0.01) and 2-year (5.17 [2.01 to 13.28], p <0.01) mortality. In conclusion, our series from a nontransplant center suggests that patients who survive the implant have acceptable short-term survival, even if they do not have a transplant option; thus, carefully selected patients with biventricular failure may benefit from an LVAD implant, even if an RVAD is needed.

The Impact of MOMENTUM 3 Trial Eligibility on Left Ventricular Assist Device Outcomes: A Real-World Experience.

INTRODUCTION: Although the landmark MOMENTUM 3 trial was associated with excellent short-term left ventricular assist device (LVAD) outcomes, many end-stage heart failure patients would not have met the trial eligibility criteria. Moreover, the outcomes of trial ineligible patients are poorly characterized. Therefore, we undertook this study to compare MOMENTUM 3 eligible and ineligible patients. METHODS: We conducted a retrospective review of all primary LVAD implants from 2017 to 2022. Primary stratification was according to MOMENTUM 3 inclusion and exclusion criteria. Primary outcome was survival. Secondary outcomes included complications and length of stay. Multivariable Cox proportional hazards regression models were constructed to further characterize outcomes. RESULTS: From 2017 to 2022, 96 patients underwent primary LVAD implantation. Thirty-seven (38.54%) patients were trial eligible while 59 (61.46%) were ineligible. When stratified by trial eligibility, patients who were trial eligible had higher 1-year (80.15% versus 94.52%, P = 0.04) and 2-year survival (70.17% versus 94.52%, P = 0.02). Multivariable analysis showed that trial eligibility was protective of mortality at both 1 y (HR: 0.19 [0.04-0.99], P = 0.049) and 2 y (HR: 0.17 [0.03-0.81], P = 0.03). Although the groups had similar rates of bleeding, stroke, and right ventricular failure, trial ineligibility was associated with a longer periprocedural length of stay. CONCLUSIONS: In conclusion, the majority of contemporary LVAD patients would not have been eligible for the MOMENTUM 3 trial. Ineligible patients have decreased but acceptable short-term survival. Our findings suggest that a simply reductionist approach to short-term mortality may improve outcomes but fail to capture the majority of patients who could benefit from therapy.

Novel Estimates of Renal Function are Associated with Short-Term Left Ventricular Assist Device Outcomes.

INTRODUCTION: Although preoperative kidney function has been associated with left ventricular assist device (LVAD) outcomes, most previous estimates of glomerular filtration rates (eGFRs) have utilized race in the calculation. Recently, novel eGFR equations independent of race have been suggested and validated. Therefore, we undertook this study to evaluate the predictive value of a novel, non-race-based eGFR calculation on short-term LVAD outcomes. METHODS: We conducted a retrospective review of all primary LVAD implants from 2017 to 2022 at our institution. eGFR was calculated using the novel Chronic Kidney Disease Epidemiology Collaboration 2021 formula (CKD-EPI 2021). eGFR was also calculated according to the Modification of Diet in Renal Disease equation for historical reference. Primary stratification was by eGFR: ≥60, 30-60, and <30. The primary outcome was 1-y survival. Multivariable Cox proportional hazards regression modeling was used to further evaluate the impact of kidney function on 1-y mortality. RESULTS: From 2017 to 2022, 91 patients underwent LVAD implantation with a HeartMate 3 device. The average age was 65.20 ± 11.08, 77 (84.62%) were male, and 14 (15.38%) were Black. The mean CKD-EPI 2021 eGFR was 56.07 ± 23.55 compared with 54.72 ± 26.37 as calculated by Modification of Diet in Renal Disease (P = 0.719). Overall, 30-d and 1-y survival was 96.7% and 85.0%, respectively. When stratified by eGFR, there was a significant difference in 1-y survival (≥60, 93.46%; 30-60, 87.36%; <30, 62.75%; P = 0.016). On multivariable analysis, a preoperative eGFR <30 was associated with an increased hazard of 1-y mortality (5.58 [1.06-29.17], P = 0.043). CONCLUSIONS: In conclusion, non-race-based estimates of renal function are predictive of short-term LVAD outcomes. Further investigation of this phenomenon is warranted.

Temporary Right Ventricular Assist Device Support for Acute Right Heart Failure: A Single-Center Experience.

INTRODUCTION: Severe right ventricular (RV) failure is associated with significant morbidity and mortality. Although right ventricular assist devices (RVADs) are increasingly used for refractory RV failure, there is limited data on their short- and long-term outcomes. Therefore, we undertook this study to better understand our experience with temporary RVADs. METHODS: We conducted a retrospective review of all RVADS performed from 2017 to 2021. Patients supported with surgical RVADs, the Protek Duo device, and the Impella RP device were included. Patients were stratified by the type of RVAD and by etiology of RV failure. Survival was assessed by the Kaplan-Meier method and multivariable Cox proportional hazards regression models. RESULTS: From 2017 to 2021, 42 patients underwent RVAD implantation: 32 with a Protek Duo, 6 with an Impella RP, and 4 with a surgical RVAD. Majority of patients were already supported with an alternate form of mechanical support. Most patients had impaired renal function, decreased hepatic function, and lactic acidosis at the time of cannulation. The median duration of RVAD support was 8.5 [5-19] d. Survival to decannulation was 68.4%, to discharge was 47.4%, and to 1-y was 40.2%. Multivariable analysis identified elevated total bilirubin levels to be associated with 30-d mortality while increased hemoglobin levels were protective. After RVAD cannulation, the median number of pressors and inotropes was lower (P < 0.01) and the lactic acidosis was less (P < 0.01). CONCLUSIONS: In conclusion, RVAD support is associated with lower lactate levels, and decreased number of vasoactive medications, but is associated with significant morbidity and mortality.

Elderly Patients With Higher Acuity Have Similar Left Ventricular Assist Device Outcomes as Younger Patients at a Nontransplant Center.

Although left ventricular assist device (LVAD) implantation is associated with acceptable survival, previous reports have demonstrated that advanced age is associated with increased short-term mortality. Because age is a relative contraindication to transplantation, nontransplant centers tend to implant a disproportionate number of elderly patients. We undertook this study to evaluate the impact of advanced age on LVAD outcomes at a nontransplant center. We conducted a retrospective review of all LVAD implants at our center from 2017 to 2022. Primary stratification was by age >70 years. The primary outcome was survival as assessed by the Kaplan-Meier method. The risk of 1-year mortality was further evaluated using multivariable Cox proportional hazards regression modeling. From 2017 to 2022, 93 patients underwent LVAD implantation. The mean age was 65.03 ± 11.28 years, with a median age of 68 (60 to 73) years. Most patients were INTERMACS 1 or 2 (71 patients; 76.34%). When stratified by age, 41 patients (44.09%) were aged ≥70 years. Patients aged ≥70 years had similar 30-day (96.15% vs 100.00%, p = 0.213), 1-year (90.05% vs 84.00%, p = 0.444), and 2-year survival (82.03% vs 84.00%, p = 0.870). When only the INTERMACS 1 and 2 patients with higher acuity were included, there was still no difference in 30-day, 1-year, or 2-year survival. On multivariable analysis, age >70 years was not associated with an increased hazard of 1-year mortality (0.90 [0.22 to 3.67], p = 0.878). In conclusion, in carefully selected patients, age >70 years is not associated with increased short-term mortality. Age alone should not be a contraindication to LVAD therapy.

Impact of preoperative Impella support on destination left ventricular assist device outcomes.

BACKGROUND: Although left ventricular assist device (LVAD) implantation is associated with improved heart failure survival, the impact of pre-implantation Impella support on outcomes is unknown. We undertook this study to evaluate the impact of preoperative Impella support on LVAD outcomes. METHODS: We conducted a retrospective review of all Heartmate 3 LVAD implants. Primary stratification was by the need for preoperative Impella support with the 5.0/5.5 device. Longitudinal survival was assessed by the Kaplan-Meier method. Multivariable Cox proportional hazards regression models were developed to evaluate mortality. Secondary outcomes included changes in laboratory values during Impella support. RESULTS: From 2017 to 2021, 87 patients underwent LVAD implantation. Sixteen were supported with a single inotrope, 36 with dual inotropes, 27 with Impella, and 3 with extracorporeal membrane oxygenation (ECMO). When stratified by the need for Impella, there was no difference in survival at 30-days (98.3 [88.2-99.8]% vs. 96.3 [76.5-99.5]%, p = .59), 1-year (91.0 [79.8-96.2] vs. 74.9 [51.7-88.2], p = .10), or at 2 years (87.9 [74.3-94.5] vs. 74.9 [51.7-88.2], p = .15). On multivariable modeling, the need for preoperative Impella was not associated with an increased hazard of 1-year (1.24 [0.23-6.73], p = .81) or 2-year mortality (1.05 [0.21-5.19], p = .95). After 7 (5-10) days of Impella support, recipient creatinine (p < .01), creatinine clearance (p = .02), and total bilirubin (p = .053) improved and lactic acidosis resolved (p < .01). CONCLUSIONS: Preoperative Impella support is not associated with increased short or long-term mortality but is associated with improved renal and hepatic function as well as total body perfusion before LVAD implantation.

Impact of Preoperative Liver Function on Short-Term HeartMate 3 Outcomes.

Although left ventricular assist device (LVAD) therapy is associated with improved survival, the impact of preoperative liver function on short-term outcomes is unclear. We conducted a retrospective review of all primary HeartMate 3 LVAD implants at a single center. Composite metrics of hepatic function including the model for end-stage liver disease (MELD), the MELD with sodium, and the MELD excluding international normalized ratio (MELD-XI) were evaluated. Receiver operator characteristic curves were compared to determine which equation was most predictive of 1-year survival. Primary stratification was based on MELD-XI tertiles. Secondary stratification was based on hypoalbuminemia (<3.0 mg/100 ml). A total of 94 patients underwent primary LVAD implantation from 2017 to 2022. MELD-XI and hypoalbuminemia were most associated with 1-year outcomes. When stratified by MELD tertiles, higher MELD was strongly associated with decreased 30 days (100.00% vs 100.00% vs 90.32%, p = 0.04), 1-year (93.00% vs 93.32% vs 69.79%, p = 0.01), and 2-year survival (93.00% vs 83.21% vs 69.79%, p = 0.04). In addition, while hypoalbuminemia was associated with similar 30 days (97.87% vs 95.74%, p = 0.56) survival, it was associated with a significant decrease in 1-year (92.93% vs 77.92%, p = 0.03) and 2-year survival (92.93% vs 68.89%, p <0.01). These results persisted on multivariable analysis for both MELD-XI score (p = 0.04) and hypoalbuminemia (p = 0.04). In conclusion, this is the first study to demonstrate that preoperative MELD-XI score and serum albumin levels are associated with short-term HeartMate 3 outcomes.

Development of a non-transplant left ventricular assist device program.

INTRODUCTION: Although the established long-term benefit of left ventricular assist device (LVAD) therapy has led to its proliferation as destination therapy (DT), few studies have evaluated LVAD outcomes at nontransplant centers. We undertook this study to better evaluate our experience in building a nontransplant, DT LVAD program. METHODS: We conducted a retrospective review of all LVADs implanted from 2010 to 2021. Patient, operative, and outcome data were extracted from the electronic medical record. Secular trends were evaluated by organizing the data into eras of implant. Survival was assessed using the Kaplan-Meier method. Multivariable Cox proportional hazards regression models further evaluated outcomes. RESULTS: From 2010 to 2021, 100 primary LVAD implants were performed. Annual volume grew from 1 to 30 implants per year. The average age of our cohort was 65.7 years, most patients (80%) were male, 51% had an ischemic etiology, and 65 (65%) were INTERMACS profile 1 or 2. Our 1- and 2-year survival were 82% and 79%, respectively. Multivariable analysis of 1-year mortality demonstrated that decreasing renal function and increased cardiopulmonary bypass (CPB) time were associated with increased mortality while preoperative hemoglobin was protective. When stratified by era of implant, our most recent patients were more likely to be INTERMACS profile 1 or 2; had shorter CPB and aortic cross clamp times; required fewer reoperations for bleeding; and suffered less right ventricular failure requiring mechanical support. CONCLUSIONS: A single, nontransplant LVAD center can experience significant growth in volume in a high-acuity cohort while maintaining acceptable outcomes and quality of care.

Clinical characteristics and 30-day outcomes in patients with acute decompensated heart failure: Results from Indian College of Cardiology National Heart Failure Registry (ICCNHFR).

BACKGROUND: Acute decompensated heart failure (ADHF) is a challenging medical emergency with high mortality and its prevalence is increasing in India. There is paucity of data on ADHF in the country. METHODS: Indian College of Cardiology National Heart Failure Registry (ICCNHFR) is an on-going observational registry on ADHF contributed by 22 hospitals across India; and we present the in-hospital and 30-day outcomes of ADHF patients enrolled from August 2018 to July 2019. Major objective included capturing demographics, comorbid conditions, aetiology, prescription patterns and assessing clinical outcomes. RESULTS: Of 5269 patients (mean age: 61.90 ± 13.85 years) enrolled in this study, males were predominant (67.09%). Mean duration of hospitalization was 5.74 ± 4.74 days. Ischemic heart disease was the most common (75.44%) aetiology. Abnormal electrocardiogram readings were found in most patients (89.86%). LVEF of ˂40% was found in 68.29% of patients. In-hospital mortality rates were 6.98%. The 30-day cumulative mortality was 12.35% and 30-day rehospitalization rate was 7.98%. At discharge, all guideline-based medical therapy (GDMT) were prescribed only to 24.99% of patients and 23.72% adhered to the prescription until 30 days. Older age, high serum creatinine levels and poor LVEF contributed to high mortality and rehospitalization. CONCLUSION: Patients with ADHF were younger and predominantly males. Usage of GDMT in ADHF patients was low (24.99%) and the in-hospital mortality was high. Older age, high serum creatinine levels, poor LVEF contributed for 30-day mortality and rehospitalization. This data on ADHF, could help in developing strategies to improve outcomes for HF patients in India.

Variations in Mitral Valve Leaflet and Scallop Anatomy on Three-Dimensional Transesophageal Echocardiography.

BACKGROUND: Textbook depictions of the mitral valve (MV) often illustrate it as composed of a single nonscalloped anterior leaflet, with the posterior leaflet having three symmetric and evenly spaced scallops. However, common variations in this anatomy have been noted in autopsy series for decades. Improved cardiac imaging with three-dimensional transesophageal echocardiography (TEE) now affords the ability to detect variations in scallop anatomy in vivo. The aims of this study were to catalog variations in mitral anatomy and to examine for association with mitral regurgitation in patients referred for clinical three-dimensional TEE. METHODS: Three-dimensional transesophageal echocardiographic images of the MV from 107 subjects were reviewed for MV variations. Three-dimensional analysis software was used to characterize mitral leaflet anatomy and assess the relative sizes of posterior leaflet scallops. RESULTS: Variations from the classic MV configuration were seen in 58.9%. Symmetric variations in the posterior leaflet (dominant P2 scallop, accessory P2 scallop, absent P2 scallop, and dichotomous P2 scallop) were seen in 33.6% of the study group. Asymmetric variants in the posterior leaflet (fused P1 and P2, fused P2 and P3, commissural scallop, accessory scallops, dichotomous P1 or P3, and dominant P2 or P3) were seen in 24.3%. Indentations or folds in the anterior leaflet were noted in 5.6%. Leaflet variations were not associated with patient demographics, indication for TEE, mitral regurgitation, mitral annular dimensions, or Carpentier class. CONCLUSIONS: Mitral leaflet morphologic variants were well characterized using three-dimensional TEE. Variants are common and were present with a frequency consistent with autopsy series. Mitral scallop variations were not associated with mitral regurgitation.

Impact of Sacubitril/Valsartan on Patient Outcomes in Heart Failure: Evidence to Date.

With an estimated 6.2 million adults affected in the USA, heart failure remains a leading cause of morbidity, mortality, and health-care costs, despite the use of guideline-based medical therapies. The search for a more efficient therapy was rekindled when findings from the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial demonstrated evidence for cardiovascular and mortality benefit of sacubitril/valsartan, a dual angiotensin receptor blocker and neprilysin inhibitor (ARNI), over enalapril (an angiotensin-converting enzyme inhibitor) in patients with heart failure and reduced rjection fraction (HFrEF). Following the trial's compelling results, recommendations for the use of sacubitril/valsartan as a replacement for an angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker were incorporated into the 2016 American College of Cardiology (ACC), the American Heart Association (AHA), and the Heart Failure Society of America recommended (HFSA) guidelines for the management of heart failure. This review aims to gain insight into the benefits as well as limitations associated with the use of sacubitril/valsartan in the treatment of heart failure (HF) through exploration of various subgroup analyses of the PARADIGM-HF trial, subsequent retrospective analyses, and randomized controlled trials that followed this landmark trial.

How to assess the severity of heart failure?

PURPOSE OF REVIEW: Mortality rates for acute decompensated heart failure and cardiogenic shock remain unacceptably high despite advances in medical therapy and mechanical circulatory support. Systems designed to quickly and accurately identify and risk stratify these patients are needed in order to improve survival. RECENT FINDINGS: The Society for Cardiovascular Angiography and Interventions developed an expert consensus statement aimed at early identification and assessment of patients with advanced heart failure and cardiogenic shock. Recent studies have validated this novel classification system within several large patient cohorts. SUMMARY: Assessing the severity of heart failure is a critical step in enabling the targeting of appropriate therapies to the appropriate patients. A novel classification system allows for accurate and reproducible identification and risk stratification.

Sudden Cardiac Death in Brugada Syndrome.

The Brugada syndrome is an inherited channelopathy that alters the main transmembrane ion currents that constitute the cardiac action potential. These changes not only modify the resting electrocardiogram but also predispose patients to develop malignant ventricular tachyarrhythmias that can lead to syncope, cardiac arrest, and sudden cardiac death. This syndrome is responsible for nearly 20% of all sudden cardiac deaths in patients with structurally normal hearts and up to 12% of all sudden cardiac deaths. Brugada syndrome is diagnosed by its characteristic electrocardiogram consisting of a coved-type ST-segment elevation of at least 2 mm followed by a negative T wave in either one of the right precordial leads. These changes can be observed spontaneously or after administration of a sodium channel blocker. While our understanding of this disease has increased tremendously since its first description in 1992, the primary therapeutic option remains implantation of an implantable cardioverter-defibrillator to avoid sudden cardiac death. Therefore, tremendous effort is being made to effectively risk stratify patients to determine who would benefit from implantable cardioverter-defibrillator implantation.

Genetic interactions between MTHFR (C677T), methionine synthase (A2756G, C2758G) variants with vitamin B12 and folic acid determine susceptibility to premature coronary artery disease in Indian population.

BACKGROUND: Researchers have determined that Indians face a higher risk of heart disease, despite the fact that nearly half of them are vegetarians and lack many of the other traditional risk factors. In the below-30 age group, coronary artery disease mortality among Indians is three-fold higher than in the whites in United Kingdom and ten-fold higher than the Chinese in Singapore. High levels of homocysteine have been widely linked to the early onset of heart diseases in other populations, although a definite proof among Indians is lacking, which needs to be investigated by way of screening for factors responsible for high homocysteine levels. OBJECTIVE: To screen for genetic factors responsible for hyperhomocysteinemia and the risk for premature coronary artery disease. MATERIALS AND METHODS: A total of 100 individuals with proven premature coronary artery disease and 200 age-and-sex matched controls were screened for polymorphisms in Methylenetetrahydrofolate reductase (MTHFR) (C677T) Methionine synthase (MS) genes (A2756G, C2758G), and the B12 and Folate levels were estimated. RESULTS: Results from the mutational analysis revealed that in the study group, seven individuals had a polymorphism for the C677T allele in the MTHFR gene (one homozygous and six heterozygous) (Fischer's Exact test P > 0.046) (OR: 0.2711 95% CI 0.0774 to 0.9491). Six were heterozygous for the A2756G polymorphism in the MS gene (Fischer's Exact test P > 0.0012). None showed a polymorphism at the C2758G allele in the MS gene. Four controls showed heterozygosity for the C677T polymorphism and none for the MS gene. The B12 and Folate levels were significantly lower in the study group as compared to the controls. CONCLUSIONS: It is important to know which factors determine the total homocysteine concentrations. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the total homocysteine concentrations, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors.

Premature coronary artery disease: role of free radical nitric oxide.

AIMS/OBJECTIVES: Over the last several decades, it has become amply evident that oxidative stress plays a significant role in the pathogenesis of coronary artery atherosclerosis and its complications. Relatively recent studies have demonstrated an association between increased oxidative stress and coronary artery disease. We therefore undertook this study to see the effect of free radical nitric oxide in patients with premature cardiovascular disease. METHODS AND RESULTS: The study included 50 individuals with premature coronary artery disease aged below 45 years, and 50 age- and sex-matched normal individuals for comparison. Free radical nitric oxide was estimated using the Griess reagent as previously described. Mean plasma nitric oxide was found to be high in the patient group as compared to the control group, which was found to be statistically significant at p > 0.0001. CONCLUSION: Increased NO production was present in the plasma of patients with premature coronary artery disease individuals as compared to normal controls. Since NO seems to have a role in tissue damage, high concentrations of NO could have probably given rise to the said clinical manifestations. Further studies are needed in this context as to whether the changed lifestyles in the young individuals or the type of occupation is leading to the oxidative stress and thereby to the disease.