Original Article--Clinical and Procedural Characteristics of Successful Transcatheter Device Closure of Ostium Secundum Atrial Septal Defect in Symptomatic Children Weighing <15 kg: A Retrospective Study Spanning One Decade From South India.

Objectives: This retrospective study sought to determine the feasibility of transcatheter atrial septal defect device closure in patients less than 15 kg, as well as to assess complication rates and the reasons for unsuccessful device closure. Background: In general, the risks associated with transcatheter atrial septal defect device closure are believed and reported to be relatively low, but the evidence stems from trials involving adults and older children. Current guidelines do not recommend atrial defect closure in device closure in children <15 kg, due to limited data available for feasibility and safety of device closure in this group of patients. Methods: Retrospective review of all patients who underwent elective transcatheter closure of ostium secundum atrial septal defect between September 2013 to February 2022. We excluded all children above 15 kg, as well as those with complex congenital heart defects. Major and minor complications were predefined and indications for referral were evaluated. Results: We identified 81 patients meeting criteria with a median procedural age of 3 years (1 year-8 years), and median weight of 12 kg (4-15 kg). Successful device closure was achieved in 95.1% (77/81) and in 4.9% (4/81), the procedure was aborted. There was 1 major (1.2%) and 1 minor (1.2%) complication, total complication rate (2.4%). 100% of the referrals had right heart enlargement and exertional dyspnoea, 18.5% had recurrent lower respiratory tract infection and 9.9% had failure to thrive. Rate of resolution of residual shunt was 95.1%. at post-procedure day 1 and 98.8% at post-procedure 3 and 6 months respectively. Conclusions: Percutaneous atrial septal defect closure can be done effectively and safely in symptomatic children weighing less than 15 kg in experienced centres. However, deferral for closure until the historically established timeline of around 4-5 years of age should be strongly considered in asymptomatic children.

Investigation of mutation spectrum amongst patients with familial primary cardiomyopathy using targeted NGS in Indian population.

Genetic cardiomyopathies (CM) are disorders that affect morphology and function of cardiac muscle. Significant number of genes have been implicated in causing the phenotype. It is one of the leading genetic causes of death in young. We performed a study to understand the genetic variants in primary cardiomyopathies in an Indian cohort. Study comprised of 22 probands (13 with family history) representing hypertrophic (n = 10), dilated (n = 7), restrictive (n = 2) and arrhythmogenic ventricular(n = 3) cardiomyopathies. Genomic DNA was target captured with a panel of 46 genes and libraries sequenced on Illumina platform. Analysis identified, reported pathogenic as well as novel pathogenic (n = 6) variants in 16 probands. Of the 10 HCM patients, candidate variants were identified in nine of them involving sarcomere genes (62%, MYBPC3, MYH6, MYH7, MYL3, TTN), Z-disc (10%, ACTN2, LDB3, NEXN,), desmosome (10%, DSG2, DSP, PKP2) cytoskeletal (4%, DTNA) and ion channel (10% RYR2). In four DCM patients, variants were identified in genes NEXN, LMNA and TTN. Three arrhythmogenic right ventricular cardiomyopathy (ARVD) patients carried mutations in desmosome genes. Rare TTN variants were identified in multiple patients. Targeted capture and sequencing resulted in identification of candidate variants in about 70% of the samples which will help in management of disease in affected individual as well as in screening and early diagnosis in asymptomatic family members. Amongst the analysed cases, 22% were inconclusive without any significant variant identified. Study illustrates the utility of next-generation multi-gene panel as a cost-effective genetic testing to screen all forms of primary cardiomyopathies.

Echocardiography protocol and cardiometabolic phenotyping in Indian birth cohorts-the IndEcho study.

Background: Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India. Methods: The IndEcho study captured transthoracic echocardiographic measurements of cardiac structure and function from 2,322 men and women aged 43-50 years. M-mode measurements in the parasternal long axis (PLAX) and 2-dimensional (2D) short axis recordings at the mitral valve, mid-papillary and apical level were recorded. Apical 2D recordings of two- three- and four-chamber (2C, 3C and 4C) views and Doppler images (colour, pulsed and continuous) were recorded in cine-loop format. Left ventricular (LV) mass, LV hypertrophy, and indices of LV systolic and diastolic function were derived. Results: Echocardiographic measurements showed good/excellent technical reproducibility. Hetero-geneity across sites, sex and rural/urban differences in cardiac structure and function were observed. Overall, this cohort of South Asian Indians had smaller LV mass and normal systolic and diastolic function when compared with published data on other Asian Indians and the West, (LV mass indexed for body surface area: Delhi men: 68 g/m2, women 63.9; Vellore men: 65.8, women 61.6) but were within ethnic-specific reference ranges. The higher prevalence of obesity, diabetes and hypertension is reflected by the higher proportion of LV remodelling and lesser hypertrophy. Conclusions: Our study adds to scarce population-based echocardiographic data for mid-life Asian Indians. Compared to published literature on other ethnic groups, the Asian Indian heart is characterised by smaller cardiac dimensions and normal range systolic and diastolic function on a background of a high prevalence of hypertension, diabetes and cardiac disease at a relatively young age. This data will form the basis for further analyses of lifecourse, metabolic and body composition predictors of cardiac structure and function, and echocardiographic predictors of future mortality. ISRCTN registration number: 13432279.

Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome.

BACKGROUND: Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES: We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS: The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS: The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.

Outcomes of Percutaneous Intervention in Patients With Takayasu Arteritis.

BACKGROUND: The status of vascular lesion treatment using percutaneous intervention (PI) in Takayasu arteritis (TAK) remains unresolved. OBJECTIVES: This study sought to develop PI strategies appropriate for TAK. METHODS: A prospectively maintained single-center database of TAK PI procedures from 1996 to 2022 was analyzed retrospectively. Obstructive lesions were treated by elective stenting (using bare or covered stents), balloon angioplasty (BA), or cutting-balloon angioplasty (CBA), with adjunctive stenting for suboptimal BA or CBA results. PIs were repeated in restenotic lesions until sustained success was obtained. Aortic or peripheral aneurysms and spontaneous aortic dissections were treated with covered stents or endografts. Immunosuppressive therapy, started before PI, was continued long term. RESULTS: A total of 942 patients underwent PI to treat 2,450 arterial lesions (2,365 stenoses or occlusions, 85 aneurysms or dissections) in 630 subclavian or axillary, 586 renal, 463 aortic, 333 carotid, 188 mesenteric, 116 iliac, 71 coronary, and 63 other arteries; 3,805 PIs were performed (1.55 PIs per lesion; range 1-7 PIs per lesion). Early success was obtained in 2,262 (92.3%), and late success in 1,460 (84.5%) of 1,727 lesions with a median of 39 months (IQR: 15-85 months) of follow-up. Repeated PIs increased late success in obstructive lesions from 48.6% to 83.3%. A total of 1,687 elective stenting lesions achieved 88% late success with 1.49 PIs per lesion; covered stents (1.18 PIs per lesion) restenosed less than bare stents (1.51 PIs per lesion; P < 0.001). A total of 183 (36%) of 513 BA-treated lesions had good outcomes without adjunctive stenting; 122 CBA-treated lesions had 19% dissections and 8% ruptures or pseudoaneurysm formations. Aneurysms or dissections had 91.3% late success after PI. A total of 472 complications occurred in 415 (17%) lesions; 375 (79%) were resolved. CONCLUSIONS: Most vascular lesions in TAK can be effectively, safely, and durably treated using predominantly stent-based PI strategies.

Spontaneous delayed expansion of self-expanding stents in stenotic arteries in Takayasu arteritis.

PURPOSE Despite frequent use of self-expanding stents (SES) in treating obstructive arterial lesions in Takayasu arteritis (TA), spontaneous delayed stent expansion (SDSE) in TA remains unstudied. This study aimed primarily to document and quantify SDSE and secondarily to determine factors that might be associated with this process. METHODS Consecutive TA patients with obstructive arterial lesions undergoing routine percutaneous intervention involving SES use (sized 1:1 with normal vessel diameter but dilated only to 4mm/5mm) were recruited prospectively. Final stent diameters obtained were measured at 1cm intervals along the length of the stent using fluoroscopic images and an indwelling marker catheter. At angiographic follow-up, stent diameters were measured again in identical fashion. Interval change in stent diameter at each point was averaged for each stent. In a small sub-study intravascular ultrasound was used at follow-up to obtain potential mechanistic insights. RESULTS Seventeen TA patients (age 33 ± 13 years, 15 female) had 22 arterial obstructive lesions (16 occlusions, 18 subclavian) treated with one SES each. Follow-up obtained in all patients after 8.7 ± 3.8 months (range 3-18 months) showed interval increase in mean stent diameter of 1.6 ± 0.5 mm, range 0.7-2.8 mm (P < 0.001); 36% of stents achieved 100% of the nominal diameter at follow-up, while 90% of stents achieved ≥90%. The degree of SDSE did not correlate with the segment of artery stented or with TA disease activity at baseline. Intravascular ultrasound in four lesions showed that SDSE was associated with positive medial-adventitial remodelling and that neointimal hyperplasia occurs concurrently, causing in-stent luminal narrowing. CONCLUSION SDSE, to diameters equal or close to nominal, occurs in all stenotic TA lesions treated with SES. The degree of SDSE does not correlate with the segment of artery stented or with TA disease activity at baseline. Preliminary results suggest that the mechanism by which SDSE is accommodated by the arterial wall is by positive medial-adventitial remodelling.

A System for Accurate Deployment of Unconstrained Triple-Fenestrated Aortic Arch Endografts.

PURPOSE: To achieve accurate rotational orientation and the axial position of unconstrained triple-fenestrated physician-modified endografts upon deployment in the aortic arch during total arch thoracic endovascular aortic repair (TA-TEVAR). MATERIALS AND METHODS: Following a detailed study of reconstructed computerized tomography angiography images of patients' arch anatomy, customized, sealable fenestrations with radio-opaque margins are created onsite on Valiant Captivia (Medtronic) endografts, transposing the arch branch ostial anatomic interrelationship onto the endograft precisely. Radio-opaque figure-of-8 markers, indicating the 12 o'clock (superior) position, are attached to the endograft on the surface and brought up to the surface under the endograft cover during resheathing. Resheathing without any twist in the endograft is achieved by lining up the welds in each endograft stent segment in a straight line. The fluoroscopic working view for arch endograft delivery and deployment is the left anterior oblique view that is orthogonal to the plane of the arch, which, in turn, is the right anterior oblique view in which parts of a stiff indwelling guidewire in the ascending and descending aorta precisely overlap. During introduction in the working view, the endograft delivery system is rotated in the descending thoracic aorta so that the 12 o'clock figure-of-8 markers are viewed on the edge and situated at the outer aortic curvature; continued advancement into the arch without any further rotation will ensure superior orientation of the figure-of-8 markers and, consequently, correct endograft rotational orientation. Proper axial endograft positioning requires locating the left common carotid artery (LCCA) fenestration just proximal to a taut externalized LCCA-femoral guidewire loop marking the posterior limit of the LCCA ostium. After endograft deployment during rapid cardiac pacing, the target arch branches are cannulated through their respective fenestrations using hydrophilic 0.035-inch guidewires that are externalized via distal sheaths to create femoral-arch branch (through-and-through) loops over which covered fenestrated stents are introduced and deployed. RESULTS: This technique was used successfully in 31 consecutive patients undergoing TA-TEVAR; systemic blood pressure was obtained in all arch branches immediately after endograft deployment, indicating adequate blood flow. All arch branches were successfully cannulated and stented. CONCLUSION: This system enables accurate deployment of unconstrained triple-fenestrated arch endografts simply and reliably during TA-TEVAR.

Takayasu Arteritis: JACC Focus Seminar 3/4.

Takayasu arteritis is a rare idiopathic large-vessel vasculitis that typically affects young women. An early "prepulseless" stage is often missed, associated with nonspecific constitutional symptoms (fever, malaise, and weight loss) and elevated inflammatory markers. Unchecked disease progression leads to the "pulseless" stage, manifest clinically by missing pulses, vascular tenderness, and ischemic symptoms (limb claudication, dizziness, angina, and renovascular hypertension), and is characterized pathologically by arterial wall thickening and stenotic/occlusive lesions or aneurysm formation. Vascular complications (stroke, blindness, heart failure, and aneurysm rupture) could follow unless disease progression is halted by immunosuppressive therapy and critical lesions are palliated by timely endovascular therapy or open surgery. Early diagnosis, effective therapy, and lifelong surveillance for disease activity relapses and vascular disease progression are critical to successful long-term outcomes. The outlook for patients has improved significantly in recent years with the establishment of diagnostic and classification criteria, better investigational modalities, and more effective medical and invasive therapy.

Patent foramen ovale closure in India; Feasibility, challenges and mid-term outcomes.

Patent foramen ovale closure (PFO) is an underutilized therapy, and our study explored the challenges and feasibility of PFO closure in the Indian setting. Eighty patients with Embolic Stroke of Undetermined Source (ESUS) were screened by transcranial Doppler (TCD) for PFO. Twenty-nine patients underwent successful closure. High-risk features of a long tunnel, inter-atrial septal aneurysm, and large defect were present in 31%, 28%, and 59%. Transcranial Doppler had a sensitivity and specificity of 78% and 53% (p = 0.02) to detect PFO. Anticoagulation was withdrawn in 85% of patients post closure. Two patients had residual shunts at follow-up of 19 (9,34) months.

Coronary artery disease management and cost implications with fractional flow reserve guided coronary intervention in Indian patients with stable ischemic coronary artery disease.

OBJECTIVES: To study the safety of stent avoidance, frequency of change in management decisions, and its cost implications while using a fractional flow reserve (FFR)-guided treatment strategy for intermediate-grade coronary artery stenosis. BACKGROUND: The impact of FFR in guiding management decisions and its cost implications has not been studied after imposition of a ceiling on stent prices by the Government of India. METHODS: In 400 patients with 477 intermediate-grade coronary lesions for whom coronary intervention was planned, functional assessment using FFR was done. Incidence of the primary composite endpoint (major adverse cardiac event [MACE], cardiac death, myocardial infarction, objective evidence of ischemia, and target vessel revascularization) in the stent avoided subset was compared with the stented group at follow-up. Micro-costing analysis was done using a computed model with current stent and FFR wire prices. RESULTS: The overall incidence of MACE was 4.9%, 0.9% in the stent-avoided subset and 6.9% in stented group (p = 0.04, comparing the latter two) at a median follow-up of 21 months (interquartile range 12-31 months). Serious adverse events occurred only in 1% of patients receiving adenosine. The average cost saving was Indian rupees (INR) 51,847 [United States Dollar (USD) 746] per patient, resulting in total savings of INR 15,813,379 (USD 227,530). Cost savings persisted but were lower by 36% (INR 18,613/USD 268 per patient) after the ceiling of stent prices. CONCLUSION: FFR-guided percutaneous coronary intervention (PCI) strategy is safe and cost-effective in countries where majority of patients self-finance their health care, resulting in stent and PCI avoidance in approximately one in three patients referred for coronary angioplasty.

Endografts with mini-cuff-augmented fenestrations for endovascular repair of thoracoabdominal aortic and common iliac artery aneurysms.

OBJECTIVE: To report a technique of creating mini-cuff-augmented fenestrations in endografts for use in endovascular aneurysm repair. METHODS: Circular fenestrations are made in Dacron thoracic (Valiant Captivia, Medtronic) or tapered iliac limb (Endurant, Medtronic) endografts using thermal cautery and the edges are strengthened with radio-opaque wire sutured on with 6-0 polypropylene. Straight thin-wall expanded polytetrafluoroethylene vascular graft of the same diameter as the fenestration is affixed to its edge with nonlocking 5-0 polypropylene suture, everted, trimmed, balloon-dilated to its nominal diameter and prevented from invaginating by relaxed external stay sutures. Mini-cuff-augmented fenestrations are often pre-cannulated with looped or externalized nitinol guidewires to facilitate catheter crossing. Successful use of mini-cuff-augmented fenestrations is illustrated in a symptomatic patient with Crawford extent-3 thoracoabdominal aortic and bilateral common iliac artery aneurysm undergoing endovascular repair. Seven mini-cuff-augmented fenestrations were created to preserve flow into five visceral arteries (celiac, superior mesenteric, left and dual right renal; all arising from the aneurysm) and both internal iliac arteries (arising at the aneurysm edge). RESULTS: Effective sealing was achieved immediately at all mini-cuff-augmented fenestrations. At 6-month follow-up there were no endoleaks, all fenestration stents were patent and undistorted, and the aneurysm sac size had decreased. CONCLUSION: Mini-cuff-augmented fenestrations accomplish effective fenestration sealing, despite being in aneurysmal zones, while preserving the advantages of fenestrations over cuffed branches.

Peripartum cardiomyopathy: An analysis of clinical profiles and outcomes from a tertiary care centre in southern India.

Peripartum cardiomyopathy is a syndrome of maternal heart failure with decreased left ventricular ejection fraction affecting maternal and fetal well-being. We analysed clinical profiles and outcomes in women with peripartum cardiomyopathy enrolled retrospectively from a tertiary care centre in southern India (1 January 2008-31 December 2014). The incidence of peripartum cardiomyopathy was one case per 1541 live births. Fifty-four women with a mean age of 25.5 years and mean gestational age of 35.4 weeks were recruited; 35 were primigravidae. Maternal and fetal deaths occurred in 9.3% and 24.1% of subjects, respectively. Mild-to-moderate maternal anaemia (80-110 g/L) was associated with fetal mortality (p = 0.02). Reduced left ventricular ejection fraction (<30%, p = 0.04) and cardiogenic shock (p = 0.01) were significantly associated with adverse maternal outcomes. Forty per cent of women were followed up after 24.2 ± 17.7 months, and in these women a significant increase in left ventricular ejection fraction was seen (mean 16.4%, p < 0.01); all were asymptomatic. Peripartum cardiomyopathy with poor left ventricular ejection fraction and shock is associated with adverse maternal outcomes, while non-severe maternal anaemia predisposes to adverse fetal outcomes. Significant left ventricular ejection fraction recovery occurred on follow-up.

Closure of the patent foramen ovale in patients with embolic stroke of undetermined source: A clinical expert opinion and consensus statement for the Asian-Pacific region.

Recently published long-term data from randomized controlled trials have provided evidence for the prevention of recurrent embolic stroke of undetermined source by percutaneous closure of the patent foramen ovale. However, most data were obtained from Caucasian populations and evidence on patent foramen ovale closure in Asian-Pacific patients is limited. The relative paucity in clinical data from this population, as well as the fact that Asian-Pacific patients may have higher bleeding risks than Caucasians, complicates clinical decision-making. This document, resulting from a consensus meeting of Asian-Pacific clinical experts, states the consensus among these experts about how to treat Asian-Pacific patients who had an embolic stroke of undetermined source and have a patent foramen ovale, based on currently available evidence and expert opinions. In addition, uncertainties and the need for clinical data regarding patent foramen ovale closure for prevention of recurrent embolic stroke of undetermined source in general, and specifically for Asian-Pacific patients, are identified.

Electrocardiographic Predictors of Mortality in Acute Anterior Wall Myocardial Infarction With Right Bundle Branch Block and Right Precordial Q-Waves (qRBBB).

BACKGROUND: Published data on the clinical, electrocardiographic, and angiographic profile of acute anterior-wall ST-elevation myocardial infarction (STEMI) with right bundle branch block with q in leads V1, V2 (qRBBB) are scarce. The aim of this study was to estimate the incidence of short-term mortality and in-hospital complications in acute qRBBB STEMI and identify the electrocardiographic (ECG) predictors of a poor outcome. METHODS: We conducted a single-centre retrospective study among the patients with acute anterior-wall STEMI and qRBBB pattern on ECG. All relevant clinical and treatment data were collected from the electronic medical records. All the ECGs taken during the index hospitalization were subjected to detailed analysis. RESULTS: Among the 272 qRBBB patients included in the study, 64% had thrombolysis in myocardial infarction (TIMI) risk score of ≥6, and 41% were in Killip class III or IV at the time of presentation. The in-hospital mortality rate was 42.6%. There was a high incidence of ventricular tachyarrhythmias (12%), complete heart block (13%), heart failure (69%), and cardiogenic shock (52%). Extreme deviation of mean QRS axis to the right (180 to 269 degrees) in the baseline ECG was associated with high in-hospital mortality (odds ratio: 13.43; 95% confidence interval: 1.48-122.03; P = 0.021). CONCLUSIONS: Acute qRBBB myocardial infarction is a sinister form of acute coronary syndrome that entails high in-hospital mortality and morbidity, necessitating early recognition and prompt institution of reperfusion therapy. Extreme deviation of QRS axis to the right (180 to 269 degrees) is a significant electrocardiographic predictor of in-hospital mortality.

Cerebral Protection Using Percutaneous Normothermic Bilateral Antegrade Cerebral Perfusion During Total Arch TEVAR in a Patient With Shaggy Aorta.

Purpose: To report a technique of global cerebral embolic protection (CEP) designed for use during thoracic endovascular aortic repair (TEVAR). Technique: Arterial cannulas are inserted percutaneously in the right axillary artery (12-F) and left common carotid artery (LCCA; 10-F) to provide normothermic antegrade cerebral perfusion during TEVAR with neuromonitoring. Inferior vena cava blood is drawn using a 19-F femoral cannula, filtered, oxygenated, and delivered through independent roller pumps to the arterial cannulas. Static CEP is obtained by balloon occlusion of the 3 aortic arch branches proximally, resulting in complete separation of aortic and cerebral blood flow; static CEP is used during aortic endograft delivery and deployment. Dynamic CEP, obtained by creating flow reversal in the innominate artery and proximal LCCA, is used at all other times. Successful use of this CEP technique is illustrated in a patient with shaggy aorta undergoing fenestrated total arch TEVAR. Conclusion: Percutaneous normothermic bilateral antegrade cerebral perfusion provides effective CEP during TEVAR.

Type 3 Coronary Perforation on Optical Coherence Imaging.

OCT imaging revealed a 1.5 mm-long transmural breach in a segment of the artery devoid of calcium or eccentric plaque burden. Focal negative remodeling identified on OCT was deemed the reason for this otherwise unexplained cause of coronary rupture.