Heterotypic electrostatic interactions control complex phase separation of tau and prion into multiphasic condensates and co-aggregates.

Biomolecular condensates formed via phase separation of proteins and nucleic acids are thought to perform a wide range of critical cellular functions by maintaining spatiotemporal regulation and organizing intracellular biochemistry. However, aberrant phase transitions are implicated in a multitude of human diseases. Here, we demonstrate that two neuronal proteins, namely tau and prion, undergo complex coacervation driven by domain-specific electrostatic interactions to yield highly dynamic, mesoscopic liquid-like droplets. The acidic N-terminal segment of tau interacts electrostatically with the polybasic N-terminal intrinsically disordered segment of the prion protein (PrP). We employed a unique combination of time-resolved tools that encompass several orders of magnitude of timescales ranging from nanoseconds to seconds. These studies unveil an intriguing symphony of molecular events associated with the formation of heterotypic condensates comprising ephemeral, domain-specific, short-range electrostatic nanoclusters. Our results reveal that these heterotypic condensates can be tuned by RNA in a stoichiometry-dependent manner resulting in reversible, multiphasic, immiscible, and ternary condensates of different morphologies ranging from core-shell to nested droplets. This ternary system exhibits a typical three-regime phase behavior reminiscent of other membraneless organelles including nucleolar condensates. We also show that upon aging, tau:PrP droplets gradually convert into solid-like co-assemblies by sequestration of persistent intermolecular interactions. Our vibrational Raman results in conjunction with atomic force microscopy and multi-color fluorescence imaging reveal the presence of amorphous and amyloid-like co-aggregates upon maturation. Our findings provide mechanistic underpinnings of overlapping neuropathology involving tau and PrP and highlight a broader biological role of complex phase transitions in physiology and disease.

Cardiac Changes and Their Reversal Following Curative Surgery in Pheochromocytoma: PheoCard Prospective Cohort Study.

BACKGROUND: Pheochromocytoma and paraganglioma (PPGL) are catecholamine producing tumors of chromaffin cell origin, known to cause varied cardiovascular manifestations from hypertension to myocardial infarction. This study sought to objectively evaluate the cardiac changes in PPGL patients and their reversal following curative surgery. METHODS: The PheoCard study was registered in ClinicalTrials.gov (NCT05082311) and involved 35 consecutive PPGL patients managed as per standard protocol involving alpha blockade followed by curative surgery. They underwent detailed cardiac evaluation using 2D-echocardiography and speckle tracking echocardiography at the time of diagnosis, 7-10 days after alpha blockade, and at 7 days, 3 months, and 6 months after surgical removal. Age- and gender-matched essential hypertensives and healthy individuals (10 in each group) served as two control groups. RESULTS: Patients with PPGLs had significantly higher mean blood pressure, left ventricle end-diastolic dimension and volume (LVEDD, LVEDV), left ventricle end-systolic volume (LVESV), septal wall thickness, LV hypertrophy, lower mean LV ejection fraction (LVEF), early diastolic mitral annular velocity (E/A), decreased amplitude of LV longitudinal strain, and increased circumferential strain (p < 0.001) when compared with the control groups at baseline. After alpha blockade, there was marked reduction in the mean LVEDD, LVEDV, LVESV, and normalization of E/A ratio (p < 0.001) in the PPGL patients. Following curative surgery (normalization of fractionated urinary metanephrines at 7-10 days post-operatively), there was early improvement in all echocardiographic parameters and it continued to improve even at 6 months after surgery. There was marked improvement in the global longitudinal strain as seen on serial speckle tracking echocardiography with recovery of most of the segments of LV depicting the reversal of subclinical endocardial dysfunction (p < 0.001). CONCLUSION: PPGL patients despite normal systolic function have subclinical LV diastolic dysfunction which is reversed after curative surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05082311.

Long-term outcomes post chronic total occlusion intervention-implications of completeness of revascularization.

BACKGROUND: Long term clinical outcomes post chronic total occlusion (CTO) intervention may depend not only on CTO success/failure alone but also on Completeness of revascularization. OBJECTIVES: To determine long term outcomes post CTO intervention and relate them to both success versus failure and Complete Revascularization (CR) versus Incomplete Revascularization (IR). METHODS: Consecutive patients taken up for CTO intervention with at-least one CTO vessel between Jan 2006 to Dec 2015 were included. Clinical, procedural and follow up details were recorded in a pre-specified custom made software. Primary endpoint of the study was survival free of major adverse event individual, death, myocardial infarction (MI), repeat revascularisation (percutaneous coronary intervention [PCI], or coronary artery bypass grafting (CABG) and recurrent or continued angina. Each individual adverse event was considered as a secondary end point. RESULTS: A total of 632 patients were enrolled in study with follow up data available in 549 (86%) constituting the study group with 490 (89.3%) success and 59 (11.7%) failure. Complete revascularization (CR) was obtained in 410 (74.7%). Follow up was median 2.9 years with inter-quartile range 1.1-4.8 years. Kaplan Meier survival analysis showed a better EFS with both CTO success versus failure (P = 0.03)and CR versus IR (P = 0.017). Individual adverse outcomes however were not significantly different in CTO success versus failure group but significantly better when analyzed with respect to CR versus IR including death (P = 0.049) and recurrent angina (P = 0.024). Repeat intervention and MI were not different by either analysis. CONCLUSIONS: Successful CTO PCI results in a better long term event free survival but the difference between the groups is more if analyzed with respect to completeness of revascularization rather than CTO success/failure alone.

Immediate impact of percutaneous transvenous mitral commisurotomy on right ventricle longitudinal strain in patients of mitral stenosis.

BACKGROUND: Right ventricular (RV) function has prognostic value in terms of survival and symptoms in patients with mitral stenosis (MS). The aim of the study was to assess RV function by strain analysis in the patients of mitral stenosis and the effect of percutaneous transvenous mitral commisurotomy (PTMC) on it. METHODS: Eighty patients of severe mitral stenosis without overt right heart failure and normal sinus rhythm undergoing PTMC were included. Conventional echocardiography and RV function by TDI-derived longitudinal strain and strain rate were assessed prior and 24 hours post PTMC and compared with 40 healthy age-matched controls. RESULTS: Eighty subjects (mean age 31 + 10 years, 70% females) were included. Patients with MS had significantly lower RV strain of basal and mid-free wall, tricuspid annular plane systolic excursion (TAPSE), and RV fractional area change (FAC) as compared to controls. There was a significant increase in pre- and post-PTMC in TAPSE (19.5 ± 2.7 mm vs 21.4 ± 3.3 mm; P < 0.001), RV basal free wall longitudinal strain (-24.4 + 6.1% vs -27.7 + 5.8%; P < 0.001), and right ventricle mid-free wall longitudinal strain (-25.6 + 5.5% vs -28.6 + 5.1%; P < 0.001), respectively. There was no significant change in RV Tei index (0.43 + 0.06 vs 0.41 + 0.03; P = 0.06). There was a significant negative correlation between RV longitudinal strain and right ventricle systolic pressure, left atrium diameter, RV Tei index, and pulmonary capillary wedge pressure, and positive correlation between RV FAC and RV TAPSE. CONCLUSION: Patients with severe MS with normal RV systolic function had decreased RV strain, which was significantly increased after a successful PTMC with reduction in afterload.

Do practice gaps exist in evidence-based medication prescription at hospital discharge in patients undergoing coronary artery bypass surgery & coronary angioplasty?

BACKGROUND & OBJECTIVES: Prescription patterns of guideline-directed medical therapy (GDMT) after coronary artery bypass surgery [coronary artery bypass graft (CABG)] and percutaneous coronary intervention (PCI) at hospital discharge are often not optimal. In view of scarce data from the developing world, a retrospective analysis of medication advice to patients following CABG and PCI was conducted. METHODS: Records of 5948 patients (post-PCI: 5152, post-CABG: 796) who underwent revascularization from 2010 to 2014 at a single tertiary care centre in north India were analyzed. RESULTS: While age and gender distributions were similar, diabetes and stable angina were more frequent in CABG group. Prescription rates for aspirin 100 per cent versus 98.2 per cent were similar, while beta-blockers (BBs, 95.2 vs 90%), statins (98.2 vs 91.6%), angiotensin-converting enzyme inhibitors (89.4 vs 41.4%), nitrates (51.2 vs 1.1%) and calcium channel blockers (6.6 vs 1.6%) were more frequently prescribed following PCI. Despite similar baseline left ventricular ejection fraction (48.1 vs 51.1%), diuretics were prescribed almost universally post-CABG (98.2 vs 10.9%, P<0.001). Nearly all (94.4%) post-CABG patients received a prescription for clopidogrel. Patients undergoing PCI were much more likely to receive higher statin dose; 40-80 mg atorvastatin (72 vs <1%, P<0.001) and a higher dose of BB. INTERPRETATION & CONCLUSIONS: Significant differences in prescription of GDMT between PCI and CABG patients existed at hospital discharge. A substantial proportion of post-CABG patients did not receive BB and/or statins. These patients were also less likely to receive high-dose statin or optimal BB dose and more likely to routinely receive clopidogrel and diuretics. Such deviations from GDMT need to be rectified to improve quality of cardiac care after coronary revascularization.

Unruptured sinus of Valsalva aneurysm mimicking as right atrial tumor.

Sinus of Valsalva aneurysm is a rare congenital cardiac abnormality and is usually diagnosed when it ruptures. An asymptomatic 55-year-old male of unruptured sinus of Valsalva aneurysm of noncoronary cusp was on medical follow-up. At 2-year follow-up, there was thrombus formation in the aneurysm, mimicking right atrium tumor on 2D transthoracic echocardiography. Cardiac computed tomography showed filling defect in the aneurysm suggestive of thrombus. Considering the high risk of systemic emboli surgery was performed, and aneurysm was repaired with Dacron patch.

Transradial approach for collateral embolisation.

Significant aortopulmonary collaterals in cyanotic CHD patients require closure immediately before definitive intracardiac repair. Traditionally, the transfemoral access has been used for this purpose; however in a few cases, selective and stable hooking of collaterals may be extremely difficult. We describe a case in which we used a new approach for collateral embolisation in a difficult situation.

The Association Between Small Dense Low Density Lipoprotein and Coronary Artery Disease in North Indian Patients.

Pathogenesis of coronary artery disease (CAD) is multi-factorial and several conventional risk factors have been ascribed; LDL-C being one of the important risk factor. However Indian population studies with established CAD often show LDL levels within normal range in patients with proven CAD. We hypothesized that Small dense low density lipoprotein (sdLDL) being more atherogenic might correlate more strongly to the occurrence and severity of CAD. The aim of the study was to evaluate the association between serum small dense LDL level and angiographically documented coronary artery disease. This is a cross sectional case control study in which sdLDL were measured in 126 patients with CAD and in 64 patients without CAD. Total cholesterol, HDL Cholesterol, LDL cholesterol and triglycerides were measured by standard methods along with other traditional risk factors. Direct quantitative measurement of sdLDL was done by enzymatic analysis. Mean sdLDL level was higher in patients with coronary stenosis than patients without coronary stenosis (16.3 ± 6.8 vs. 10.1 ± 5.7 mg/dL respectively, (p < 0.001). There was significant correlation between mean sdLDL and severity of CAD as assessed by syntax score with mean sdLDL level in low, intermediate and high syntax score being 15.0 ± 5.8, 20.1 ± 6.7 and 22.7 ± 7.3 mg/dL respectively (p value <0.001). A cut off value of 10.02 mg/dL was associated with presence of CAD (95 % CI 0.82-0.93, p < 0.001) using ROC curve. In conclusion Indian patients with established CAD have higher sdLDL levels compared to individuals without CAD despite having comparable LDL levels.

An elephant trunk appearance-what is the diagnosis?

Coronary cameral fistula is a rare congenital cardiac abnormality. An 18-year-old boy presented with features of right heart volume overload. Clinical examination was suggestive of hyperdynamic circulation with continuous murmur in precordium. 2D echocardiography showed dilated right coronary artery, and 3D echocardiography added information in tracing the track of the fistula which was consistent with the diagnosis of right coronary cameral fistula draining into the right ventricle. Coronary angiograms revealed an unusually dilated right coronary artery giving the appearance of an "elephant trunk" and with a fistulous tract into the right ventricle. Considering the higher risks of surgery in such difficult cases, we performed a successful transcatheter closure of the fistula using an Amplatzer vascular plug.

Assessment of endothelial dysfunction in Asian Indian patients with chronic kidney disease and changes following renal transplantation.

BACKGROUND: Endothelial dysfunction may explain increased cardiovascular risk in patients with chronic kidney disease (CKD). METHODS: Brachial artery was imaged during reactive hyperemia (endothelium-dependent, flow-mediated dilatation, FMD) and during glyceryl trinitrate-mediated dilatation (nitroglycerine-mediated dilatation, NMD, endothelium-independent) in 108 patients with CKD and three months following renal transplantation (RT) in 60 of them. RESULTS: Patients with CKD had significantly lower FMD vs. controls (9.1% vs. 18.3%, p < 0.001) while NMD was comparable (19.8% vs. 21.8%, p = ns). Impaired FMD (<4.5%) was observed in 26.8% patients with CKD and was more common in those on hemodialysis (HD; 28.4% vs. 15.4%) vs. those not on dialysis. FMD for patients with glomerular filtration rate (GFR) 15-60 vs. <15 mL/min/1.73 m(2) was 12.9% and 8.8% (p = 0.05; respectively -29% and -52% lower vs. controls), indicating reduced FMD with increasing CKD severity. There was +72% increase in FMD following RT (9.1 to 15.7%, p < 0.001) while mean NMD was unchanged. Following RT, only 3.3% had impaired FMD. CONCLUSIONS: Patients with CKD have endothelial dysfunction as evidenced by reduced FMD. Decreased FMD indicating worsening endothelial function was noted with increasing severity of CKD. Within three months of RT, there was significant improvement in FMD, while NMD values did not change.

Does high dose statin pretreatment affect global strains in patients undergoing valve replacement.

Purpose: To study the effect of rosuvastatin 40 mg (initiated 7 days prior to surgery) in patients undergoing valve replacement (VR) for rheumatic mitral valve disease on left ventricular (LV) strain and biomarker release kinetics. Methods: In this randomized study, cardiac biomarkers viz. troponin I (TnI), Creatine kinase MB (CK-MB), N-terminal pro B-type natriuretic peptide (NTPBNP) were measured before surgery; and 8, 24 and 48 h postoperatively. Global LV (circumferential, global circumferential strain (GCS); longitudinal, GLS; radial, global radial strain (GRS)) strains were measured preoperatively; and 48 h and 30 days postoperatively. Results: Following VR, Global Longitudinal Strain (GLS), Global Circumferential Strain (GCS) and Global Radial Strain (GRS) declined at 48 h in both statin loaded (SL) and non loaded (NL) groups. The %decline in strain was significantly lower in SL group (% change in GLS 35.8% vs 38.8%, GCS 34% vs 44.1%, GRS 45.7% vs 52.6%; p < 0.001).All strain values improved at 30 days with higher improvement in SL group (GLS -15.92 ± 2.00% vs -12.6 ± 1.66%, GCS -15.12 ± 2.93% vs -13.04 ± 2.44%; GRS 22.12 ± 6.85% vs 19.32 ± 6.48%). While TnI, CKMB, NTPBNP increased following surgery, values at 8, 24 and 48 h were lower in the SL vs. NL group. Mean change (baseline to peak biomarker value) was also significantly lower in SL group.The SL group had shorter hospital and Intensive Care Unit (ICU) stay. On Receiver Operating Characteristic Curve (ROC) analysis, baseline GCS ≤ 14% best predicted postoperative 30 day Left Ventricular Ejection Fraction (LVEF) ≤ 50%. Conclusion: Pre-operative high dose rosuvastatin was "cardioprotective" with favorable effect on LV global strain and release kinetics of biomarkers. These cut-offs (described for the first time for rheumatic VR) can be used as prognostic predictors.

RAdiation Dose Attenuation using RADPAD in CATH lab for primary and secondary operators - RADAR-CATH STUDY.

Background: Radiation injury is an important concern for interventional cardiologists and needs to be addressed. RADPAD is a radiation protection drape that has been shown to reduce the radiation exposure of the primary operator (PO). While Indian data on radiation exposure of the PO in the cath lab are scarce, the exposure of the secondary operator (SO) is even less well studied. Aims: The aim of this study was to evaluate the efficacy of RADPAD drapes in reducing radiation doses in the cath lab for the primary as well as the secondary operator. Methods: A total of 160 patients (40 patients each with single vessel disease [SVD], double vessel disease [DVD] and triple vessel disease [TVD] undergoing coronary angioplasty, and 40 patients undergoing balloon mitral valvuloplasty [BMV]) were randomised in a 1:1 pattern to undergo a procedure with or without the use of RADPAD. Results: For patients with SVD, DVD and TVD undergoing percutaneous coronary intervention (PCI) and those undergoing BMV, the % reduction with the use of RADPAD reduced the PO's received dose (in mrem) by 65%, 54%, 28% and 67%, respectively, as compared to without RADPAD. The % reduction in relative operator exposure for the PO for the 4 groups was 55%, 34%, 18% and 75%, respectively, with the use of RADPAD. The corresponding % reduction for the SO's received dose (in mrem) was 80%, 63%, 33% and 69% and for relative operator exposure was 74%, 46%, 23% and 76% in the 4 groups, respectively. Conclusions: RADPAD significantly reduces the radiation exposure of the primary and secondary operator during prolonged complex PCI and BMV procedures.

Metabolic syndrome & Framingham Risk Score: observations from a coronary angiographic study in Indian patients.

BACKGROUND & OBJECTIVES: Metabolic syndrome (MS) is an important determinant of cardiovascular (CV) risk. Framingham Risk Scores (FRS) often underestimate the CV risk in Asians, younger patients and those with MS. Asians often develop coronary artery disease (CAD) at a younger age and also have a high prevalence of MS. Only limited data are available on the relationship between MS and FRS in such patients and the present study was undertaken to report on this aspect in an Indian patient population with angiographically documented CAD. METHODS: Two hundred patients undergoing coronary angiography during a three months study period were included. Diagnosis of MS was based on modified south Asian guidelines. RESULTS: Of the 200 patients (age 56.5 ± 8.6 yr) undergoing coronary angiography, MS was diagnosed in 77 per cent n=154; abdominal obesity, low HDL and hypertension were the commonest of the diagnostic criteria of MS, being present in >70 per cent cases. Patients with MS had significantly higher mean FRS than those without MS (15.1 vs 8.65, P<0.0001). Most patients with MS (74%, n=148) had an intermediate to high 10-year CV risk (>10%) as estimated by FRS. The proportion of patients with MS progressively increased in those with low, intermediate and high FRS (61, 87 and 92%, respectively). Though the prevalence of MS was uniformly similar (74-84%) in all age groups (<45, 45-55, 55-65 and > 65 yr, respectively), amongst those <45 yr, none of the patients could be categorized as having high CV risk as estimated by FRS despite having angiographic CAD, highlighting the limitation of age dependence of FRS. INTERPRETATION & CONCLUSIONS: MS is common in Indian patients with angiographically documented CAD; most patients with MS have 10-year risk of >10 per cent as estimated by FRS. Though MS is uniformly prevalent across all age groups, using the FRS may underestimate the CV risk in Indian patients despite documented CAD. These findings have significant implications for Asian patients with CAD in whom onset of CAD is often at a younger age than their Western counterparts. There should be continued health care emphasis on detection of MS and intensification of targeted preventive strategies.

Comparison of non-invasive assessment for pulmonary vascular indices by two-dimensional echocardiography and cardiac computed tomography angiography with conventional catheter angiocardiography in unrepaired Tetralogy of Fallot physiology patients weighing more than 10 kg: a retrospective analysis.

AIMS: Assessment of pulmonary vascular dimensions (PVDs) in Tetralogy of Fallot (TOF) is an integral part of planning transcatheter and surgical interventions. We sought to examine the reliability and correlation of echocardiography (ECHO) and computed tomography angiography (CTA) measurements with those obtained by cardiac catheterization and angiography (CCA). METHODS AND RESULTS: Tetralogy of Fallot physiology patients undergoing ECHO, CTA, and CCA within a month prior to surgical correction during 2018-2020 were retrospectively enrolled. Indexed diameter of pulmonary annulus (iPAnn), indexed right pulmonary artery (iRPA), indexed left pulmonary artery (iLPA) and indexed descending aorta (iDA) were measured using ECHO and CTA followed by derivation of Nakata index (NI), McGoon's ratio (MGR), ratio of predicted peak right ventricular (RV) and left ventricular (LV) pressures (pRV/pLV) and Z-scores. Comparison with CCA-derived measurements was made and correlational equations were subsequently deduced. Pulmonary vascular dimensions for 54 patients with mean age of 15.5 ± 9.3 years (range: 3-34 years) were analysed. Computed tomography angiography and CCA measurements for iPAnn, iRPA, NI, MGR, pRV/pLV, and Z-score were comparable with each other while ECHO parameters were significantly lower than CCA. However, iLPA diameter was significantly underestimated by ECHO and overestimated by CTA. Correlational analysis showed stronger correlation between CTA- and CCA-derived PVD as against ECHO measurements except for iDA, pRV/pLV, and Z-score. CONCLUSIONS: For unrepaired TOF physiology patients weighing more than 10 kg, CTA-acquired PVD are reliable and comparable with CCA except for DA for which ECHO is non-inferior. Non-invasive modalities though are inferior to CCA for LPA sizing. Utilizing derived equations, precise estimation of PVD can be carried out using non-invasive tools.

Flecainide for conversion and maintenance of sinus rhythm after mitral valve replacement in rheumatic atrial fibrillation.

BACKGROUND: Despite successful mitral valve replacement (MVR), many patients remain in AF. Flecainide can be useful in these patients but has not been used because of underlying structural heart disease. METHODS: We assessed oral flecainide for conversion and maintenance of SR in 25 patients of chronic rheumatic AF following MVR (age 34.4 yrs, mean AF duration: 3.6 yrs). Non-converters underwent DC cardioversion at 24 h and 4 weeks. Patients received flecainide and bb/diltiazem at discharge. RESULTS: Single oral dose of Flecainide achieved SR in 6/25 (24%) while 19/25 achieved SR after DCC; at24 h 21/25 (84%) were in SR. With mean flecainide dose (93.10 ± 9.40 mg), successful maintenance of SR at 6 months was seen in 16/23 (69.5%). No significant changes in PR interval, QRS duration or QTc were noted; flecainide was well tolerated. Patients in SR had significantly better functional status, QOL scores and higher LA strain at 6 months (25.25 vs 17.43%, p < .0001). Baseline LA diameter ≤ 61 mm predicted SR at 6 months (sensitivity/specificity 93.7% and 85.71%) while the values for AF duration ≤ 4 years and LA strain > 21% for predicting SR were 87.5/71.43% and 100/85.71% respectively. CONCLUSION: Oral flecainide was safe and effective in post MVR rheumatic AF patients; maintenance of SR was achieved in 76% of initial converters and 64% of overall population, with better LA strain values. More studies are needed to validate these results.

A pilot study evaluating the role of ivabradine for rate control in patients with rheumatic atrial fibrillation.

OBJECTIVES: Ivabradine may have a role in rate control of atrial fibrillation (AF) due to effects on HCN channels in AV node. We studied role of Ivabradine in rate control of rheumatic AF. METHODS: 80 patients, rheumatic AF, HR > 100 bpm (age 47 ± 11 yrs, AF duration 6.8 ± 2.9 years, rate 131 ± 16 bpm) on maximally tolerated ßß or CCB's, randomized to Ivabradine or escalated ßß/CCB. Ivabradine started @ 2.5 mg BD; increased to 5 mg BD if inadequate response at 1 week (failure to decrease HR < 10% vs baseline). After Holter at 1 month, dose escalated to 7.5 mg BD if needed. RESULTS: Ivabradine resulted in significantly lower HR (81 ± 10 vs 99 ± 9) at 3 months and 6 months (79 ± 8 vs 94 ± 8, p < 0.001). Absolute reduction in HR: 56 ± 15 vs 31 ± 14 bpm and % change in HR: 41 ± 7 vs 24 ± 9%, both p < 0.00001). At 6 months, Ivabradine group had. 1Significantly lower NT Pro BNP (1168 vs 1314 pg/ml), higher 6 min walk distance (410 ± 47 vs 349 ± 54 m, all p < 0.001) 2Better symptom class (EHRA score 1: asymptomatic 84% vs 40%), improvement >1 EHRA class; baseline 60% vs 17% 3Better LA Strain (22.8 ± 2.8% vs 20.6 ± 2.5%) Ivabradine was well tolerated and there was no drug withdrawal. CONCLUSION: Our data suggest that Ivabradine can be an option for rate control in rheumatic AF.

Tracking the path traversed by temporary pacing lead.

Persistent left superior vena cava (PLSVC) results from abnormal development of the sinus venosus in the early stages of fetal life. Though there are numerous reports of successful permanent pacemaker implants in such cases, placement of permanent pacing leads in such cases is technically challenging, often requiring shaping of stylets and considerable lead maneuvering. We describe an interesting case wherein a temporary pacemaker lead after entering the PLSVC followed an unusual fluoroscopic course with demonstrable pacing in right ventricle (RV), right atrium (RA) and the left ventricle (LV). Interventional cardiologists and intensivists performing pacing procedures need to be aware that one may rarely encounter such interesting radiographic and electrocardiographic patterns in these cases with anomalous systemic venous drainage.

Is Indexed Left Atrial Volume (LAVi) in Indian Patients with Acute Coronary Syndrome (ACS) undergoing revascularization a predictor of cardiovascular outcomes?

BACKGROUND: Left atrial volume indexed to body surface area (LAVi) is the recommended method for LA size quantification. Assessing LAVi in Indian patients undergoing coronary interventions for acute coronary syndrome (STEMI, NSTEMI, and UA) is clinically relevant. METHODS AND RESULTS: Amongst 190 patients (66.4 yrs, 68.4% males), 29.5%, 40.5%, and 30% respectively had STEMI, NSTEMI and UA. Mean LAVi was 32.29 ± 12.06 ml/m2 and 111 (58.4%) had LAVi ≥32 while 79 (41.6%) had LAVi <32. Patients were divided into 2 groups (group 1 LAVi >32 and group 2 LAVi <32). Group 1 patients had higher prevalence of TVD [n = 49 vs n = 5, p = <0.001] and higher mean Syntax score (24.47 vs 14.64, p = <0.001). Despite similar LVEF, those with higher LAVi had had higher incidence of mild MR (50.4 vs 27.8, P = 0.0002) and moderate/severe MR was present only in Group 1 patients (27.9% and 5.4%). Grade I, II, and III diastolic dysfunction was present in 71.2, 17.1, and 9.9% patients in Group 1 vs 45.6%, 0%, and 0% in group 2. Diastolic parameters like septal E/e' and lateral E/e'ratio were also higher in Group 1. Major adverse cardiovascular events (MACE) at 30 days was significantly higher in group 1 (20.7 vs 6.3%, P = 0.006). On multivariate analysis, triple vessel disease and LAVi were the only predictors of MACE while LVEF was not. ROC curve analysis for LAVi demonstrated that a cut-off 33.35 ml/m2, predicted 30 day MACE with Area under curve (AUC) 0.775 (95% CI 0.700-0.850); sensitivity and specificity of 86.7% and 61.4%. Inter-quartile analysis of LAVi (<26.3, 26.3-33.35, 33.36-36.3, and >36.3 ml/m2) demonstrated that 30 day MACE increased across quartiles (4.16%, 4.25%, 22.44%, and 28.26%, respectively, P < 0.001). CONCLUSION: Amongst patients with ACS undergoing revascularization, those with higher LAVi had more severe CAD, diastolic dysfunction and higher 30 day MACE. LAVi provides superior prognostic information as compared to conventional LV systolic and diastolic parameters in patients with ACS and should be incorporated in routine echocardiographic analysis. More studies with larger numbers and longer follow up are required to further elucidate on this.

Neutrophil Gelatinase-Associated Lipocalin as a Marker for Contrast-Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention: A Prospective Observational Analysis.

Introduction: Incidence of contrast-induced nephropathy (CIN) post percutaneous coronary intervention (PCI) varies between 5% and 20%. Neutrophil gelatinase-associated lipocalin (NGAL) is a sensitive marker for acute kidney injury. Data regarding the predictive accuracy of NGAL in Indian patients undergoing PCI is sparse. Methods: A total of 212 consecutive "all-comer" patients, undergoing PCI from March 2015 to April 2016 were recruited in this single-center observational study. Plasma NGAL levels were measured at 4 hours post PCI using commercially available enzyme-linked immunosorbent assay (Triage® Alere™, San Diego, CA, USA). Results: Twenty-five (11.8%) patients developed CIN. The 4-hour post-PCI plasma NGAL levels were significantly higher in patients with CIN than without (400.6 ± 269.3 ng/mL vs. 109.8 ± 68.0 ng/mL, P < 0.0001). Patients developing CIN had higher age, low estimated glomerular filtration rate (eGFR), and higher contrast volume usage during PCI. After adjusting for confounding factors, diabetes mellitus (adjusted odds ratio [AOR] 3.04; P = 0.039; 95% confidence interval [CI]: 1.06-8.73), hypotension at presentation (AOR 24.84; P < 0.0001; 95% CI: 4.65-132.83), and multi-staged PCI (AOR 13.45; P < 0.0001; 95% CI: 4.54-39.79) were found to independently predict the development of CIN. NGAL levels significantly correlated with age (r = 0.149, P = 0.031), eGFR (r = -0.385, P < 0.0001), hemoglobin (r = -0.214, P = 0.002), contrast volume (r = 0.185, P = 0.007), and 48-hour post-PCI serum creatinine levels (r = 0.334, P < 0.0001). At a cutoff of 256.5 ng/mL, plasma NGAL had a sensitivity of 68% and a specificity of 95.2% (area under the curve = 0.878; P < 0.0001; 95% CI: 0.801-0.955) to predict the occurrence of CIN. Conclusions: Plasma NGAL is an early and highly predictive biomarker of CIN in patients undergoing PCI. Patients having diabetes, hypotension at presentation and those undergoing second-stage procedures are at a high risk of developing CIN after PCI.