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.

A case of Kartagener’s syndrome: Importance of early diagnosis and treatment.

Kartagener’s syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. Primary ciliary dyskinesia is a genetic disorder with manifestations present from early life and this distinguishes it from acquired mucociliary disorders. Approximately one half of patients with primary ciliary dyskinesia have situs inversus and, thus are having Kartagener syndrome. We present a case of 12 year old boy with sinusitis, situs inversus and bronchiectasis. The correct diagnosis of this rare congenital autosomal recessive disorder in early life is important in the overall prognosis of the syndrome, as many of the complications can be prevented if timely management is instituted, as was done in this in this case.

A case of Kartagener's syndrome: Importance of early diagnosis and treatment.

Kartagener's syndrome is a very rare congenital malformation comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. Primary ciliary dyskinesia is a genetic disorder with manifestations present from early life and this distinguishes it from acquired mucociliary disorders. Approximately one half of patients with primary ciliary dyskinesia have situs inversus and, thus are having Kartagener syndrome. We present a case of 12 year old boy with sinusitis, situs inversus and bronchiectasis. The correct diagnosis of this rare congenital autosomal recessive disorder in early life is important in the overall prognosis of the syndrome, as many of the complications can be prevented if timely management is instituted, as was done in this in this case.

Association of carotid intima-media thickness with left main coronary artery disease.

BACKGROUND: Previous studies have shown that carotid intima-media thickness correlates well with the presence and extent of coronary artery disease. This study was conducted to determine whether it could reliably predict the presence of left main coronary artery disease. METHODS: Common carotid intima-media thickness was measured in 50 patients with angiographically proven significant (> or =50%stenosis) left main coronary artery disease and in another 50 age- and sex-matched patients with coronary artery disease without the involvement of the left main coronary artery. Measurements of the carotid intima-media thickness were made on the far wall 1 cm from the distal end of the common carotid artery bilaterally, and the average and the greater of the two values thus obtained for each patient were used for analysis. Plaques were not included in the measurement of carotid intima-media thickness. RESULTS: The average and greater of the two values were significantly higher in patients with left main coronary artery disease as compared to those without it (average intima-media thickness: 0.926 +/- 0.12 vs. 0.78 9 +/- 0.16 mm; p< 0.001; greater intima-media thickness: 0.994 +/- 0.13 vs. 0.844 +/- 0.20 mm; p< 0.001). The cut-off values of 0.81 mm for the average carotid intima-media thickness and 0.87 mm for the greater carotid intima-media thickness were found to have optimum sensitivity (92% and 90%, respectively) and specificity (60% and 64%, respectively) for the detection of left main coronary artery disease. A higher cut-off value of 1.0 mm increased specificity to 92% and 84%, respectively, for the average and greater thicknesses, but sensitivity decreased markedly. CONCLUSIONS: There is a significant association between increased carotid intima-media thickness and the presence of left main coronary artery disease. The measurement of carotid intima-media thickness can be used with reasonably good sensitivity and specificity for the detection of left main coronary artery disease in patients who are undergoing evaluation for suspectedcoronary artery disease.

Quadricuspid aortic valve with severe aortic regurgitation.

Quadricuspid aortic valve is a rare congenital anomaly that usually presents with aortic regurgitation. Its importance, however, lies in its association with coronary abnormalities, which may lead to surgical catastrophe, if not diagnosed pre-operatively. This report describes a case of quadricuspid aortic valve detected incidentally during routine pre-operative transesophageal echocardiography.

Low-dose dobutamine echocardiography predicts recovery of left ventricular systolic function following revascularization even in presence of low contractile reserve.

BACKGROUND: Coronary revascularization is known to improve left ventricular ejection function (LVEF) in patients with severe left ventricular systolic dysfunction if there is myocardial viability and contractile reserve is >40% as determined by low-dose dobutamine echocardiography (LDDE). We tried to assess effect of coronary revascularization on left ventricular systolic function in patients with low contractile reserve (40%). METHODS AND RESULTS: In a retrospective analysis we studied 114 consecutive patients with left ventricular systolic dysfunction (LVEF <40%) with low contractile reserve (<40%) as detected by LDDE (16-segment model). Contractile reserve was defined as number of dysfunctional segments that improved on LDDE divided by total number of left ventricular segments studied. Dysfunctional segments at baseline that improved on low-dose dobutamine were considered viable. On the basis of presence or absence of viability and treatment modality, patients were grouped as: revascularization with viability-group A; revascularization without viability-group B; medical therapy with viability-group C, and; medical therapy without viability-group D. At subsequent follow-up (3 months, 1 year and 2 years) left ventricular systolic function was assessed by LVEF and wall motion score index (WMSI). Improvement in left ventricular systolic function was considered to have occurred only if both LVEF and WMSI showed statistically significant ( p<0.05) improvement from baseline. The mean LVEF in viable and non-viable groups were 33.3 -/+ 6.8% and 30.3 -/+ 7.1%, respectively. In patients with viability, the mean number of dysfunctional segments that improved at LDDE was 3.4 -/+ 1.7 and mean contractile reserve was 21.1 -/+ 17.8%. At LDDE, significant improvement in LVEF was seen in all four groups; however, significant improvement in WMSI was seen only in those with viability. At subsequent follow-up (3 months, 1 year and 2 years), significant improvement in LVEF and WMSI as compared to baseline was evident in group A alone. At two years, although the improvement in WMSI was of borderline significance (p = 0.05), the improvement in LVEF was significant ( p < 0.05). No significant improvement was seen in LVEF and/or WMSI in groups B, C and D. CONCLUSION: Presence of myocardial viability on LDDE predicts recovery of left ventricular systolic function even in patients with low contractile reserve which is maintained at long-term follow-up, following revascularization.

Carotid Intima-Media Thickness and Brachial Artery Flow-Mediated Dilatation in Patients with and without Metabolic Syndrome.

BACKGROUND, Metabolic syndrome has recently emerged as a marker of future cardiovascular risk. However its incremental value for this purpose, over conventional cardiovascular risk factors and diabetes mellitus in particular, is debated. The present study was conducted to determine the extent of subclinical atherosclerosis in patients with metabolic syndrome, and compare it with the same in individuals with cardiovascular risk factors not having metabolic syndrome. METHODS, A total of 156 individuals seeking outpatient cardiac consultation for various indications were included in the study and were divided into four groups - group 1: cardiovascular risk factors present but not metabolic syndrome (n = 60) : group 2 : metabolic syndrome without diabetes mellitus or coronary artery disease (n = 21) ;group 3: metabolic syndrome with diabetes mellitus without coronary artery disease ( n = 27) ;and group 4:patients with documented coronary artery disease (n = 48). Metabolic syndrome was diagnosed on the basis of Adult Treatment Panel III (ATPIII) criteria. All patients underwent assessment of carotid intima-media thickness and brachial artery flow-mediated vasodilatation. RESULTS, Both carotid intima-media thickness and brachial artery flow-mediated vasodilatation were similar in groups 1 and 2 (carotid intima-media thickness: 0.687 -/+ 0.13mm and 0.706 -/+0.23mm, p = 0.963; brachial artery flow-mediated vasodilatation: 11.80 -/+ 5.16% and 12.87 -/+ 7.04%, respectively, p =0.883) , but group 3 patients had significantly higher carotid intima-media thickness (0.774 +/- 0.15mm, p = 0.047) and significantly lower brachial artery flow-mediated vasodilatation (7.37 -/+ 6.12%, p -/+ 0.007) as compared to group 1 patients. There was no significant difference in the two parameters between groups 3 and 4 (carotid intima-media thickness in group 4:0.789 -/+ 0.16mm,p = 0.976 and brachial artery flow-mediated vasodilatation:5.86 -/+ 3.85%, p -/+ 0.709). CONCLUSIONS, In absence of diabetes mellitus, metabolic syndrome was not associated with greater extent of subclinical atherosclerosis compared to individual cardiovascular risk factors. Presence of diabetes mellitus, however, resulted in significant endothelial dysfunction and evidence of subclinical atherosclerosis, similar to that seen in patients with already established coronary artery disease.

Aneurysm of sinus of Valsalva dissecting into interventricular septum with left ventricular communication.

Septal dissection with left ventricular communication is a rare complication of aneurysm of sinus of Valsalva. This report describes a case of aneurysm of sinus of Valsalva with septal dissection, almost in its entirety with left ventricular communication--which is a very rare occurrence.

Real-time three-dimensional transthoracic echocardiography.

BACKGROUND: Complex anatomy of intra-cardiac structures requires spatial orientation of image in three dimensions for better understanding and enhanced image interpretation. We evaluated the feasibility and efficacy of the emerging 'real-time three-dimensional transthoracic echocardiography' technique for comprehensive assessment of cardiac anatomy, physiology, pathomorphology and pathophysiology in patients with structural heart disease. METHODS AND RESULTS: Patients with structural heart disease (n=152) were evaluated by conventional two-dimensional transthoracic echocardiography and real-time three-dimensional transthoracic echocardiography using standard protocol. Fifty-six cases were of rheumatic etiology with multi-valvular involvement (mitral stenosis: 32; mitral regurgitation: 29; tricuspid regurgitation: 8; aortic valve disease: 11) and 21 cases of non-rheumatic valvular heart disease. A total of 38 congenital heart disease patients were examined including 23 patients with atrial septal defect. Left ventricular function (n=20) and right ventricular function (n=10) were also assessed using dedicated software. CONCLUSIONS: Results of real-time three-dimensional transthoracic echocardiography mitral valve area assessment by planimetery are comparable to two-dimensional transthoracic echocardiography with additional information about surface anatomy of leaflets and the subvalvular apparatus in real time with clear demarcation of commissural fusion and scallops of leaflets. Enface view of atrial septal defect with direct visualization of shape, size and number of defects, tricuspid valve area by planimetery, right ventricular shape, objective assessment of ventricular volumes and regurgitation vena contracta area are the fields where three-dimensional transthoracic echocardiography was of additive value to conventional two-dimensional transthoracic echcardiography. This study proves clinical feasibility of real-time three-dimensional transthoracic echocardiography but requires further validation of quantitative observations.

Non-invasive assessment of endothelial function by brachial artery flow mediated vasodilatation and its association with coronary artery disease: an Indian perspective.

Endothelial dysfunction is the final common pathway through which various coronary risk factors culminate into atherosclerosis and subsequent coronary artery disease (CAD). Endothelial function can be reliably assessed by flow mediated vasodilatation (FMD) in the brachial artery using high-resolution ultrasonography and has been shown to be an excellent surrogate marker for the presence of CAD. Two hundred and forty-one individuals comprising of 101 patients with CAD (angiographically proven, or with history of documented myocardial infarction) and 140 individuals without CAD were included in the study. All subjects underwent clinical evaluation, fasting lipid profile, treadmill test and FMD assessment. Selected individuals underwent coronary angiography too. Brachial artery diameter and Doppler indices (systolic and diastolic velocity time integrals) were recorded using high resolution ultrasonography at baseline, immediately after and at one minute after release of cuff (occlusion time 5 minutes). FMD was calculated as percentage increase in brachial artery diameter at one minute. FMD index was calculated as the ratio of FMD and percentage increase in flow during reactive hyperaemia. Mean FMD was significantly higher in non-CAD group (8.71+/-4.77%) than in CAD group (3.77+/-2.03%; p < 0.0001). The FMD index was also significantly higher in the non-CAD group (0.031 ) than in CAD group (0.021; p=0.0117). On multiple regression analysis, FMD index was found to be significantly associated with presence of CAD (p=0.0015), independent of conventional cardiovascular risk factors. Endothelial function as assessed by FMD is significantly depressed in patients with established CAD and this association is independent of presence of conventional cardiovascular risk factors.

Carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with and without coronary artery disease.

BACKGROUND: Carotid intima-media thickness and pulse wave velocity are non-invasive markers of atherosclerosis and have been shown to reliably predict presence and extent of atherosclerotic vascular disease. However, studies examining their association with each other have shown inconsistent results. Hence it was sought to assess correlation between carotid intima-media thickness and pulse wave velocity in patients with and without coronary artery disease. METHODS AND RESULTS: Sixty-four patients with angiographically proven coronary artery disease and 84 age-matched individuals without coronary artery disease but having one or more conventional cardiovascular risk factors were included in the study. Individuals with established cerebrovascular disease and peripheral vascular disease were excluded from the study. Carotid intima-media thickness of far wall was measured at three predefined sites (distal common carotid, carotid bifurcation and proximal internal carotid artery) on each side. Brachial-ankle pulse wave velocity was measured non-invasively using VP 1000 (Colin Corporation) automated ABI/ PWV analyzer. There was no significant difference in gender and presence of cardiovascular risk factors in the two groups. Mean and maximum carotid intima-media thickness and brachial-ankle pulse wave velocity were all significantly higher in coronary artery disease patients as compared to patients without coronary artery disease (0.842 v. ( 0.657 mm, p <0.0001; 1.076 v. 0.795 mm, p <0.0001; 1708.63 v. 1547.26 cm/s, p <0.0004 respectively). There was a significant correlation between brachial-ankle pulse wave velocity and both mean and maximum carotid intima-media thickness in patients with coronary artery disease (r = 0.47, p <0.0001 and r=0.41, p < 0.0008 respectively) but not in individuals without coronary artery disease (r=0.01 and -0.1 respectively). CONCLUSIONS: Presence of significant correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity in patients with coronary artery disease but absence of the same in individuals without major atherosclerotic vascular disease suggests that the correlation between carotid intima-media thickness and brachial-ankle pulse wave velocity becomes stronger with increasing extent of atherosclerosis.

Coronary calcium and coronary artery disease: an Indian perspective.

BACKGROUND: Coronary artery calcification is a part of the development of atherosclerosis. It occurs exclusively in atherosclerotic arteries and can be used as a noninvasive marker of coronary atherosclerosis. As there is no large-scale study on coronary calcium score reported in the Indian population till date, this study was undertaken for calculating the score in Indians at intermediate-to-high risk of coronary artery disease, and to correlate it with angiographically proven coronary artery disease. METHODS AND RESULTS: A total of 388 consecutive patients who underwent coronary calcium scoring and coronary angiography were included in the study. Calcium scoring was performed based on a modification of the Agatston Score using a high-speed computed tomography scanner (GE CT/i scanner). Coronary calcium scores were correlated with the presence or absence of significant coronary artery disease (defined as > or = 70% stenosis of at least one major epicardial coronary artery) on angiography. Out of 388 patients who underwent coronary angiography, 298 were found to have significant coronary artery disease. Mean coronary calcium score was significantly higher in patients with angiographically proven coronary artery disease (226.7+/-65.2) as compared to those who had normal angiograms (20.29+/-56.7; p value<0.0001). All the 72 patients who had a score > 400 had an abnormal angiogram (sensitivity 23.1%, specificity 100%, positive predictive value 100%, and negative predictive value 24.1%). On the other hand, among the patients who had a score > 0, 298 were found to have abnormal angiograms, while 16 had normal angiograms (sensitivity 95.5%, specificity 78.9%, positive predictive value 94.9%, and negative predictive value 81.1%). CONCLUSIONS: Detection of coronary calcium score by a helical computed tomography scanner is a useful tool for predicting the presence of significant coronary artery disease in intermediate-to-high risk patients. An absolute score of 0 has a high negative predictive value for the presence of coronary artery disease, and may obviate the need to perform coronary angiogram in intermediate-risk patients. On the other extreme, score > 400 is highly predictive of the presence of coronary artery disease, and virtually confirms the presence of significant coronary artery disease in intermediate-to-high risk patients.