Publications by authors named "Ganesan Karthikeyan"

162 Publications

Efficient Dynamic Nuclear Polarization up to 230 K with Hybrid BDPA-Nitroxide Radicals at a High Magnetic Field.

J Phys Chem B 2021 Nov 24. Epub 2021 Nov 24.

Centre de RMN à Très Hauts Champs, Université de Lyon (CNRS/ENS Lyon/UCBL), 69100 Villeurbanne, France.

Pairing the spectral resolution provided by high magnetic fields at ambient temperature with the enhanced sensitivity offered by dynamic nuclear polarization (DNP) is a major goal of modern solid-state NMR spectroscopy, which will allow one to unlock ever-challenging applications. This study demonstrates that, by combining HyTEK2, a hybrid BDPA-nitroxide biradical polarizing agent, with -terphenyl (OTP), a rigid DNP matrix, enhancement factors as high as 65 can be obtained at 230 K, 40 kHz magic angle spinning (MAS), and 18.8 T. The temperature dependence of the DNP enhancement and its behavior around the glass transition temperature () of the matrix is investigated by variable-temperature EPR measurements of the electron relaxation properties and numerical simulations. A correlation is suggested between the decrease in enhancement at the passage of the and the concomitant drop of both transverse electron relaxation times in the biradical.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpcb.1c07307DOI Listing
November 2021

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease.

N Engl J Med 2021 Nov 13. Epub 2021 Nov 13.

From Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati School of Medicine - both in Cincinnati (A.B.); Uganda Heart Institute (E.O., J.R., J.A., P.L., M.N., E.N., I.O.O.), and the Department of Medicine, Makerere University (E.O.) - both in Kampala, Uganda; Children's National Hospital, Washington, DC (L.C., M. Murali, R.S., C.A.S.); Murdoch Children's Research Institute (A.G., D.E., A.C.S.), and Melbourne Children's Global Health, Royal Children's Hospital (D.E., A.C.S.), Melbourne, and Telethon Kids Institute, Perth Children's Hospital, University of Western Australia, Perth (J.C.) - all in Australia; Virginia Tech Carilion School of Medicine, Roanoke, VA (A.D.W.); Assistance Publique-Hôpitaux de Paris, Université de Paris, and Cardio-Oncologie, Hôpital Européen Georges-Pompidou - both in Paris (M. Mirabel); Instituto Nacional de Saúde, Maputo, Mozambique (A.O.M.); Universidade Federal de Minas Gerais, Belo Horizonte, Brazil (M.C.P.N.); Emory University School of Medicine, Atlanta (A.S.); Green Lane Paediatric and Congenital Cardiac Service, Starship Children's Hospital, Auckland, New Zealand (N.W.); Geisel School of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH (M.Z.); the Division of Paediatric Cardiology, Department of Paediatrics, Red Cross War Memorial Children's Hospital, and the Division of Cardiology, Department of Medicine, Groote Schuur Hospital - both in Cape Town, South Africa (L.Z.); and All India Institute of Medical Sciences, New Delhi, India (G.K.).

Background: Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown.

Methods: We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years.

Results: Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis).

Conclusions: Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMoa2102074DOI Listing
November 2021

Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population: A Pilot Study.

JACC CardioOncol 2021 Oct 19;3(4):565-576. Epub 2021 Oct 19.

Department of Cardiology, AIIMS, New Delhi, India.

Background: Prevalence of both degenerative severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CA) increases with age. Dual disease (AS+myocardial ATTR-CA) occurs in significant proportion of patients undergoing surgical aortic valve replacement (SAVR).

Objectives: This study aimed to determine the prevalence of ATTR-CA in severe AS in the Indian population, identify noninvasive predictors of its diagnosis, and understand its impact on prognosis.

Methods: Symptomatic severe AS patients aged ≥65 years undergoing SAVR were enrolled. ATTR-CA diagnosis was based on preoperative 99m-technetium pyrophosphate (PYP) scan and intraoperatively obtained basal interventricular septum biopsy for myocardial ATTR-CA, and excised native aortic valve for isolated valvular ATTR-CA. Primary amyloidosis was excluded by serum/urine protein electrophoresis with serum immunofixation.

Results: SAVR was performed in 46 AS patients (age 70 ± 5 years, 70% men). PYP scan was performed for 32 patients, with significant PYP uptake in 3 (n = 3 of 32, 9.4%), suggestive of myocardial ATTR-CA. On histopathological examination, none of the interventricular septum biopsy specimens had amyloid deposits, whereas 33 (71.7%) native aortic valves showed amyloid deposits, of which 19 (57.6%) had transthyretin deposition suggestive of isolated valvular amyloidosis. Noninvasive markers of dual disease included low myocardial contraction fraction (median [interquartile range], 28.8% [23.8% to 39.1%] vs 15.3% [9.3% to 16.1%];  = 0.006), deceleration time (215 [144 to 236] ms vs 88 [60 to 106] ms;  = 0.009) and global longitudinal strain (-18.7% [-21.1% to -16.9%] vs -14.2% [-17.0% to -9.7%];  = 0.030). At 1-year follow-up, 2 patients died (4.3%); 1 each in myocardial ATTR-CA negative and positive groups (3.4% vs 33.3%;  = 0.477).

Conclusions: Dual disease is not uncommon in India. Isolated valvular amyloidosis in severe AS is much more common.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaccao.2021.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551518PMC
October 2021

Early intervention for asymptomatic mitral stenosis: a stitch in time?

Heart 2021 12 7;107(24):1931-1932. Epub 2021 Oct 7.

Cardiology, All India Institute of Medical Sciences, New Delhi, India

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2021-319987DOI Listing
December 2021

Detecting sub-clinical disease activity in patients with chronic rheumatic valvular heart disease.

Indian Heart J 2021 May-Jun;73(3):313-318. Epub 2021 Feb 27.

Department of Cardiology, All India Institute of Medical Sciences (AIIMS), New Delhi, India. Electronic address:

Objective: Valve disease progression in rheumatic heart disease(RHD) is generally attributed to recurrent attacks of acute rheumatic fever(ARF). However, persistence of chronic sub-clinical inflammation remains a plausible but unproven cause. Non-invasive means to identify sub-clinical inflammation may facilitate research efforts towards understanding its contribution to disease progression.

Methods: Patients with chronic RHD, without clinical evidence of ARF, undergoing elective valve surgery were enrolled. Sub-clinical inflammation was ascertained by histological evaluation of left atrial appendage and valve tissue excised during surgery. We assessed the diagnostic utility of Gallium-67 scintigraphy imaging, and inflammatory biomarkers, hsCRP, IL-2, IL-6, Tumor Necrosis Factor-Alpha(TNF-α), Interferon-gamma(IFN-γ), and Serum Amyloid A(SAA), in identifying patients with sub-clinical inflammation.

Results: Of the 93 RHD patients enrolled(mean age 34 ± 11 years, 45% females), 86 were included in final analysis. Sub-clinical inflammation was present in 27 patients(31.4%). Patients with dominant regurgitant lesions were more likely to have sub-clinical inflammation compared to those with stenotic lesions, though this association was not statistically significant(dominant regurgitant lesions vs isolated mitral stenosis: OR 3.5, 95%CI 0.68-17.96, p = 0.133). Inflammatory biomarkers were elevated in the majority of patients: hsCRP, IL-2, IL-6, TNF-α, and IFN-γ in 44%, 89%, 90%, 79%, and 81% patients, respectively. However, there was no significant association between biomarker elevation and histologically ascertained sub-clinical inflammation. Ga-67 imaging was unable to identify inflammation in the 15 patients in whom it was performed.

Conclusion: Sub-clinical inflammation is common in RHD patients. Conventional inflammatory markers are elevated in the majority, but aren't discriminatory enough to identify the presence of histologic inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ihj.2021.02.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322815PMC
October 2021

Cardiovascular clinical examination: the need for an evidence-based approach.

Eur Heart J 2021 10;42(40):4101-4102

Department of Cardiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab327DOI Listing
October 2021

Long-term oral anticoagulation for atrial fibrillation in low and middle income countries.

Indian Heart J 2021 Mar-Apr;73(2):244-248. Epub 2021 Feb 10.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

With increasing life-expectancy and changing demographics, non-valvular atrial fibrillation (AF) is currently the most common indication for long-term oral anticoagulation (OAC) in low and middle income countries (LMICs). Due to a decreasing trend in the prevalence of rheumatic heart disease (RHD), valve disease as a primary cause of AF now constitutes a small fraction of all people with AF. Moreover, emerging data also indicate that, patients with significant valve disease and AF may have a risk of stroke similar to, if not lower than, those with non-valvular AF. Previous trials of anticoagulation for AF excluded people from LMICs partly because valvular AF constituted a large proportion of those with AF, and it was thought to confer a prohibitively high risk of stroke. Trialists should therefore be less reluctant to include patients with AF from LMICs in general, and those with valve disease in particular, in future trials of anticoagulation. The quality of vitamin K antagonist based oral anticoagulation remains poor in LMICs to a large extent because of poor monitoring. The widespread use of the direct oral anticoagulants (DOAC) presents a practical approach to improve anticoagulation quality. Randomised trials of DOACs in valvular AF are particularlycriticalto bridge the knowledge gap in this area. Discussions regarding oral anticoagulation (OAC) use in low and middle income countries (LMICs) have historicallybeendominated by severallong-held beliefs. The first is that the quality of vitamin K antagonist (VKA) based anticoagulation is poor in these countries. The veracity of this assumption is supported by a large number of studies documenting both lower prescription of OACs, and a lower proportion of international normalised ratio (INR) values in the therapeutic range.The second is that a large proportion of patients receiving OAC in LMICs have atrial fibrillation (AF) related to valvular heart disease, and rheumatic mitral stenosis in particular. This assumption, perhaps valid several decades ago, is no longer supported by the data. Finally, patients with valvular heart disease and AF (specifically those with moderate or severe valve lesions), are thought to be at prohibitively high thromboembolic risk. However, recent evidence suggests that this risk may have been overestimated.Nevertheless, the aforementioned assumptions continue to contribute to the underrepresentation of patients from LMICs in clinical trials of oral anticoagulation. Knowledge of the characteristics of contemporary patients in LMICs who are eligible for long-term OAC, estimates of their stroke risk, and a better understanding of the drivers of poor anticoagulation quality, may help guide research and clinical practice. In this review, we seek to provide an evidence-based perspective on OAC use in patients with AF living in LMICs and China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ihj.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065364PMC
November 2021

Interactions between methodological and interindividual variability: How Monetary Incentive Delay (MID) task contrast maps vary and impact associations with behavior.

Brain Behav 2021 05 22;11(5):e02093. Epub 2021 Mar 22.

Department of Psychology, University of Michigan, Ann Arbor, MI, USA.

Introduction: Phenomena related to reward responsiveness have been extensively studied in their associations with substance use and socioemotional functioning. One important task in this literature is the Monetary Incentive Delay (MID) task. By cueing and delivering performance-contingent reward, the MID task has been demonstrated to elicit robust activation of neural circuits involved in different phases of reward responsiveness. However, systematic evaluations of common MID task contrasts have been limited to between-study comparisons of group-level activation maps, limiting their ability to directly evaluate how researchers' choice of contrasts impacts conclusions about individual differences in reward responsiveness or brain-behavior associations.

Methods: In a sample of 104 participants (Age Mean = 19.3, SD = 1.3), we evaluate similarities and differences between contrasts in: group- and individual-level activation maps using Jaccard's similarity index, region of interest (ROI) mean signal intensities using Pearson's r, and associations between ROI mean signal intensity and psychological measures using Bayesian correlation.

Results: Our findings demonstrate more similarities than differences between win and loss cues during the anticipation contrast, dissimilarity between some win anticipation contrasts, an apparent deactivation effect in the outcome phase, likely stemming from the blood oxygen level-dependent undershoot, and behavioral associations that are less robust than previously reported.

Conclusion: Consistent with recent empirical findings, this work has practical implications for helping researchers interpret prior MID studies and make more informed a priori decisions about how their contrast choices may modify results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/brb3.2093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119872PMC
May 2021

Comparison of the effect of Morphine and Fentanyl in patients with acute coronary syndrome receiving Ticagrelor - The COMET (Comparison Morphine, Fentayl and Ticagrelor) randomized controlled trial.

Int J Cardiol 2021 05 15;330:1-6. Epub 2021 Feb 15.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Dual antiplatelet therapy (DAPT) remains the cornerstone of acute coronary syndrome (ACS) management, and ticagrelor is one of the commonly used second antiplatelet agents. There is some evidence to suggest that morphine may reduce the antiplatelet effect of ticagrelor.

Methods And Results: In a single-center, randomized controlled trial, we compared the effect of morphine and fentanyl on platelet aggregation (PA) among patients with ACS treated with ticagrelor. Platelet aggregation was studied by automated light transmittance aggregometry (LTA) at baseline, and at 2 h after ticagrelor loading. The primary outcome was the difference in the maximal inhibition of platelet aggregation [IPA(%)] between the groups at 2 h. Pain relief, and drug-related adverse events were secondary outcomes. Of 136 patients randomized, 70 received fentanyl and 66 received morphine. At baseline, the median (IQR) platelet aggregation [61.35% (54.6 to 70) Vs. 58.8% (52.7 to 72.9)] were comparable between the groups. There was no statistically significant difference between the fentanyl and the morphine groups in IPA at 2-h [85.88%(64.65-98.16) and 81.93%(44.2-98.03), p = 0.09]. However, morphine use was independently associated with a PA of >30% at 2 h (p < 0.009). There was no difference in adverse events.

Conclusion: In patients with ACS, there was no significant difference between the use of fentanyl or morphine on the effect of ticagrelor on PA. (CTRI/2018/04/013423).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2021.02.037DOI Listing
May 2021

Metabolic Exchange and Energetic Coupling between Nutritionally Stressed Bacterial Species: Role of Quorum-Sensing Molecules.

mBio 2021 01 19;12(1). Epub 2021 Jan 19.

CNRS, Aix-Marseille University, Bioenergetic and Protein Engineering Laboratory, Mediterranean Institute of Microbiology, Marseille, France.

Formation of multispecies communities allows nearly every niche on earth to be colonized, and the exchange of molecular information among neighboring bacteria in such communities is key for bacterial success. To clarify the principles controlling interspecies interactions, we previously developed a coculture model with two anaerobic bacteria, (Gram positive) and Hildenborough (Gram negative, sulfate reducing). Under conditions of nutritional stress for , the existence of tight cell-cell interactions between the two bacteria induced emergent properties. Here, we show that the direct exchange of carbon metabolites produced by allows to duplicate its DNA and to be energetically viable even without its substrates. We identify the molecular basis of the physical interactions and how autoinducer-2 (AI-2) molecules control the interactions and metabolite exchanges between and (or and ). With nutrients, produces a small molecule that inhibits the AI-2 activity and could act as an antagonist Sensing of AI-2 by could induce formation of an intercellular structure that allows directly or indirectly metabolic exchange and energetic coupling between the two bacteria. Bacteria have usually been studied in single culture in rich media or under specific starvation conditions. However, in nature they coexist with other microorganisms and build an advanced society. The molecular bases of the interactions controlling this society are poorly understood. Use of a synthetic consortium and reducing complexity allow us to shed light on the bacterial communication at the molecular level. This study presents evidence that quorum-sensing molecule AI-2 allows physical and metabolic interactions in the synthetic consortium and provides new insights into the link between metabolism and bacterial communication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mBio.02758-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845633PMC
January 2021

Stroke risk in rheumatic heart disease.

Heart 2021 05 18;107(9):694-696. Epub 2021 Jan 18.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110029, India

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-318756DOI Listing
May 2021

Worldwide Variation in the Use of Nuclear Cardiology Camera Technology, Reconstruction Software, and Imaging Protocols.

JACC Cardiovasc Imaging 2021 09 13;14(9):1819-1828. Epub 2021 Jan 13.

Seymour, Paul, and Gloria Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, New York, USA; Department of Radiology, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, New York, USA. Electronic address:

Objectives: This study sought to describe worldwide variations in the use of myocardial perfusion imaging hardware, software, and imaging protocols and their impact on radiation effective dose (ED).

Background: Concerns about long-term effects of ionizing radiation have prompted efforts to identify strategies for dose optimization in myocardial perfusion scintigraphy. Studies have increasingly shown opportunities for dose reduction using newer technologies and optimized protocols.

Methods: Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study) registry, a multinational, cross-sectional study comprising 7,911 imaging studies from 308 labs in 65 countries. The study compared regional use of camera technologies, advanced post-processing software, and protocol characteristics and analyzed the influence of each factor on ED.

Results: Cadmium-zinc-telluride and positron emission tomography (PET) cameras were used in 10% (regional range 0% to 26%) and 6% (regional range 0% to 17%) of studies worldwide. Attenuation correction was used in 26% of cases (range 10% to 57%), and advanced post-processing software was used in 38% of cases (range 26% to 64%). Stress-first single-photon emission computed tomography (SPECT) imaging comprised nearly 20% of cases from all world regions, except North America, where it was used in just 7% of cases. Factors associated with lower ED and odds ratio for achieving radiation dose ≤9 mSv included use of cadmium-zinc-telluride, PET, advanced post-processing software, and stress- or rest-only imaging. Overall, 39% of all studies (97% PET and 35% SPECT) were ≤9 mSv, while just 6% of all studies (32% PET and 4% SPECT) achieved a dose ≤3 mSv.

Conclusions: Newer-technology cameras, advanced software, and stress-only protocols were associated with reduced ED, but worldwide adoption of these practices was generally low and varied significantly between regions. The implementation of dose-optimizing technologies and protocols offers an opportunity to reduce patient radiation exposure across all world regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2020.11.011DOI Listing
September 2021

High prevalence and a long delay in the diagnosis of primary aldosteronism among patients with young-onset hypertension.

Clin Endocrinol (Oxf) 2021 06 22;94(6):895-903. Epub 2021 Feb 22.

Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.

Background: Despite being the most common cause of secondary hypertension, prevalence of primary aldosteronism (PA) among patients with young-onset hypertension (YH - age of hypertension onset <40 years) remains poorly studied.

Objective: We assessed the prevalence of PA in patients with YH referred for evaluation of secondary hypertension.

Design And Patients: In this prospective, cross-sectional study, 202 patients with YH, visiting endocrine and cardiology clinics of All India Institute of Medical Sciences, India, were evaluated.

Measurements: Primary aldosteronism was screened by measuring plasma aldosterone concentration (PAC) and direct renin concentration (DRC) and calculating aldosterone-to-renin ratio (ARR), followed by confirmatory saline infusion test (SIT) according to Endocrine Society Guideline. Those confirmed with post-SIT PAC >5 ng/dl underwent adrenal computed tomography (CT), followed by adrenal venous sampling (AVS).

Results: Of 202 YH patients, 38 (18.8%) screened positive, and PA was confirmed in 36 (17.8%). The mean age was 43.9 ± 10.9 years, and median duration of hypertension was 10.5 (3.5-18) years. The prevalence of PA increased with grade of hypertension (8.1% in grade 1 to 37.1% in grade 3), number of antihypertensive medications (2.5% in those taking ≤1 to 50% in those taking ≥4 medications) and severity of hypokalaemia (0% in potassium >5 to 85.7% in potassium <3.5 mmol/L). The prevalence of PA by age of hypertension onset was highest in age group 30-39 years (31.3%).

Conclusions: There is a high prevalence and a long delay in diagnosis of PA among patients with YH, and YH should be considered as a separate high-risk category in PA screening algorithm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cen.14409DOI Listing
June 2021

Stroke risk prediction in patients with atrial fibrillation with and without rheumatic heart disease.

Cardiovasc Res 2021 Jan 2. Epub 2021 Jan 2.

Population Health Research Institute, McMaster University, Hamilton, Canada.

Aims: Patients with atrial fibrillation (AF) and rheumatic heart disease (RHD), especially mitral stenosis, are assumed to be at high risk of stroke, irrespective of other factors. We aimed to re-evaluate stroke risk factors in a contemporary cohort of AF patients.

Methods And Results: We analyzed data of 15,400 AF patients presenting to an emergency department and who were enrolled in the global RE-LY AF registry, representing 47 countries from all inhabited continents. Follow-up occurred at 1 year after enrollment. A total of 1,788 (11.6%) patients had RHD. These patients were younger (51.4 ± 15.7 vs. 67.8 ± 13.6 years), more likely to be female (66.2% vs. 44.7%) and had a lower mean CHA2DS2-VASc score (2.1 ± 1.7 vs. 3.7 ± 2.2) as compared to patients without RHD (all p < 0.001). Significant mitral stenosis (average mean transmitral gradient 11.5 ± 6.5 mmHg) was the predominant valve lesion in those with RHD (59.6%). Patients with RHD had a higher baseline rate of anticoagulation use (60.4% vs. 45.2%, p < 0.001). Unadjusted stroke rates at 1 year were 2.8% and 4.1% for patients with and without RHD, respectively. The performance of the CHA2DS2-VASc score was modest in both groups (stroke at 1 year, c-statistics 0.69, 95% confidence interval [CI] 0.60-0.78 and 0.63, 95% CI 0.61-0.66, respectively). In the overall cohort, advanced age, female sex, prior stroke, tobacco use and non-use of anticoagulation were predictors for stroke (all p < 0.05). Mitral stenosis was not associated with stroke risk (adjusted odds ratio 1.07, 95% CI 0.67-1.72, p = 0.764).

Conclusions: The performance of the CHA2DS2-VASc score was modest in AF patients both with and without RHD. In this cohort, moderate-to-severe mitral stenosis was not an independent risk factor for stroke.

Translational Perspective: Based on studies conducted several decades ago, the presence of moderate-to-severe mitral stenosis has been associated with a very high risk of stroke in patients with AF. Our results, based on a large, global sample of contemporary patients with AF that contained a significant proportion of individuals with RHD, challenge the assumption that mitral stenosis is a major, independent risk factor for stroke. The performance of the widely used CHA2DS2-VASc score was modest in both patients with and without RHD. At least one ongoing randomized trial is evaluating the optimal antithrombotic strategy in patients with AF and RHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvaa344DOI Listing
January 2021

Probing of heavy metals in the feathers of shorebirds of Central Asian Flyway wintering grounds.

Sci Rep 2020 12 17;10(1):22118. Epub 2020 Dec 17.

Unit of Vector Control, Phytochemistry and Nanotechnology, Department of Zoology, Annamalai University, Annamalainagar, Tamil Nadu, 608 002, India.

The study is intended to deliver the incidence of heavy metals in the feathers of shorebirds from two important Central Asian Flyway (CAF) migratory shorebirds wintering sites such as the Point Calimere Wildlife Sanctuary (PWLS) and Pichavaram Mangrove Forest (PMF), India. Feathers of fifteen species of shorebirds and seven different metals viz., Cu, Cr, Co, Pb, Hg, Ni and Zn were analyzed. Zn was highest in Dunlin, Little-ringed Plover, Marsh Sandpiper, and Common sandpiper, Ni showed highest in Little ringed plover, and Common sandpiper, Co, Cr, and Cu were maximum in Little stint, Marsh sandpiper, and Dunlin, respectively. The Hg was higher in Black-winged stilt, Common redshank, Curlew Sandpiper, Eurasian curlew, Lesser Sand-plover, Temminck's stint, Kentish plover, Spotted redshank, and Wood sandpiper, the Pb found highest in Kentish plover, Painted stork, Spotted redshank, Wood sandpiper, Eurasian Curlew, and Lesser sand-plover. The concentration of metals showed significant variations among the species of shorebirds studied (P < 0.001). The mercury negatively correlated with the other metals than the other six metals studied in both the wetlands. The order of metal concentration in the feathers of shorebirds was Zn > Ni > Co > Cr > Cu > Pb > Hg. Nevertheless, the current study revealed that the level of metals in the shorebirds is alarming; since the PWLS and PMF are located along the CAF routes, it needs intensive studies on various pollutions to manage both the resident as well as migratory shorebirds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-79029-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747699PMC
December 2020

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.

J Am Coll Cardiol 2020 12;76(25):2982-3021

University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, USA.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755038PMC
December 2020

Alternative Hypothesis to Explain Disease Progression in Rheumatic Heart Disease.

Circulation 2020 12 30;142(22):2091-2094. Epub 2020 Nov 30.

Cardiovascular Research Institute, National University of Singapore, and Genome Institute of Singapore (R.S.-Y.F.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050955DOI Listing
December 2020

Clinical and gated SPECT MPI parameters associated with super-response to cardiac resynchronization therapy.

J Nucl Cardiol 2020 Nov 5. Epub 2020 Nov 5.

Emory University, Atlanta, GA, USA.

Purpose: We sought to evaluate the behavior of cardiac mechanical synchrony as measured by phase SD (PSD) derived from gated MPI SPECT (gSPECT) in patients with super-response after CRT and to evaluate the clinical and imaging characteristics associated with super-response.

Methods: 158 subjects were evaluated with gSPECT before and 6 months after CRT. Patients with an improvement of LVEF > 15% and NYHA class I/II or reduction in LV end-systolic volume > 30% and NYHA class I/II were labeled as super-responders (SR).

Results: 34 patients were classified as super-responders (22%) and had lower PSD (32° ± 17°) at 6 months after CRT compared to responders (45° ± 24°) and non-responders 46° ± 28° (P = .02 for both comparisons). Regression analysis identified predictors independently associated with super-response to CRT: absence of previous history of CAD (odds ratio 18.7; P = .002), absence of diabetes mellitus (odds ratio 13; P = .03), and history of hypertension (odds ratio .2; P = .01).

Conclusion: LV dyssynchrony after CRT implantation, but not at baseline, was significantly better among super-responders compared to non-super-responders. The absence of diabetes, absence of CAD, and history of hypertension were independently associated with super-response after CRT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12350-020-02414-8DOI Listing
November 2020

Overestimation of Stroke Risk in Rheumatic Mitral Stenosis and the Implications for Oral Anticoagulation.

Circulation 2020 11 2;142(18):1697-1699. Epub 2020 Nov 2.

Population Health Research Institute, McMaster University, Hamilton, Canada (S.J.C., S.Y.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050347DOI Listing
November 2020

Reproducibility of global LV function and dyssynchrony parameters derived from phase analysis of gated myocardial perfusion SPECT: A multicenter comparison with core laboratory setting.

J Nucl Cardiol 2020 Oct 20. Epub 2020 Oct 20.

Emory University, Atlanta, GA, USA.

Background: Gated myocardial perfusion scintigraphy (GMPS) phase analysis is an important tool to investigate the physiology of left ventricular (LV) dyssynchrony. We aimed to test the performance of GMPS LV function and phase analysis in different clinical settings and on a diverse population.

Methods: This is a post hoc analysis of a prospective, non-randomized, multinational, multicenter cohort study. Clinical evaluation and GMPS prior to cardiac resynchronization therapy (CRT)(baseline) and 6-month post CRT (follow-up) were done. LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV ejection fraction (LVEF), LV phase standard deviation (LVPSD), and percentage of left ventricle non-viable (PLVNV) were obtained by 10 centers and compared to the core lab.

Results: 276 GMPS studies had all data available from individual sites and from core lab. There were no statistically significant differences between all variables except for LVPSD. When subjects with no mechanical dyssynchrony were excluded, LVPSD difference became non-significant. LVESV, LVEF, LVPSD and PLVNV had strong correlation in site against core lab comparison. Bland-Altman plots demonstrated good agreement.

Conclusions: The presented correlation and agreement of LV function and dyssynchrony analysis over different sites with a diverse sample corroborate the strength of GMPS in the management of heart failure in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12350-020-02397-6DOI Listing
October 2020

The American Heart Association's Call to Action for Reducing the Global Burden of Rheumatic Heart Disease: A Policy Statement From the American Heart Association.

Circulation 2020 11 19;142(20):e358-e368. Epub 2020 Oct 19.

Rheumatic heart disease (RHD) affects ≈40 million people and claims nearly 300 000 lives each year. The historic passing of a World Health Assembly resolution on RHD in 2018 now mandates a coordinated global response. The American Heart Association is committed to serving as a global champion and leader in RHD care and prevention. Here, we pledge support in 5 key areas: (1) professional healthcare worker education and training, (2) technical support for the implementation of evidence-based strategies for rheumatic fever/RHD prevention, (3) access to essential medications and technologies, (4) research, and (5) advocacy to increase global awareness, resources, and capacity for RHD control. In bolstering the efforts of the American Heart Association to combat RHD, we hope to inspire others to collaborate, communicate, and contribute.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIR.0000000000000922DOI Listing
November 2020

Dynamic Nuclear Polarization Enhancement of 200 at 21.15 T Enabled by 65 kHz Magic Angle Spinning.

J Phys Chem Lett 2020 Oct 22;11(19):8386-8391. Epub 2020 Sep 22.

Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Solid-state nuclear magnetic resonance under magic angle spinning (MAS) enhanced with dynamic nuclear polarization (DNP) is a powerful approach to characterize many important classes of materials, allowing access to previously inaccessible structural and dynamic parameters. Here, we present the first DNP MAS experiments using a 0.7 mm MAS probe, which allows us to reach spinning frequencies of 65 kHz, with microwave irradiation, at 100 K. At the highest magnetic field available for DNP today (21.1 T), we find that the polarizing agent HyTEK2 provides DNP enhancements as high as 200 at a spinning rate of 65 kHz at 100 K, and BDPA yields an enhancement of 106 under the same conditions. Fast spinning rates enable excellent DNP performance, but they also yield unprecedented H resolution under DNP conditions. We report well-resolved H-detected H-C and H-N correlation spectra of microcrystalline histidine·HCl·HO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpclett.0c02493DOI Listing
October 2020

Worldwide Diagnostic Reference Levels for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging: Findings From INCAPS.

JACC Cardiovasc Imaging 2021 03 19;14(3):657-665. Epub 2020 Aug 19.

Seymour, Paul, and Gloria Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, New York, New York, USA; Department of Radiology, Columbia University Irving Medical Center and NewYork-Presbyterian Hospital, New York, New York, USA. Electronic address:

Objectives: This study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).

Background: Reference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset.

Methods: Data were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data.

Results: The aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m-labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions.

Conclusions: This study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2020.06.029DOI Listing
March 2021

Enhanced Intersystem Crossing and Transient Electron Spin Polarization in a Photoexcited Pentacene-Trityl Radical.

J Phys Chem A 2020 Jul 9;124(29):6068-6075. Epub 2020 Jul 9.

Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.

Identifying and characterizing systems that generate well-defined states with large electron spin polarization is of high interest for applications in molecular spintronics, high-energy physics, and magnetic resonance spectroscopy. The generation of electron spin polarization on free-radical substituents tethered to pentacene derivatives has recently gained a great deal of interest for its applications in molecular electronics. After photoexcitation of the chromophore, pentacene-radical derivatives can rapidly form spin-polarized triplet excited states through enhanced intersystem crossing. Under the right conditions, the triplet spin polarization, arising from -selective intersystem crossing rates, can be transferred to the tethered stable radical. The efficiency of this spin polarization transfer depends on many factors: local magnetic and electric fields, excited-state energetics, molecular geometry, and spin-spin coupling. Here, we present transient electron paramagnetic resonance (EPR) measurements on three pentacene derivatives tethered to Finland trityl, BDPA, or TEMPO radicals to explore the influence of the nature of the radical on the spin polarization transfer. We observe efficient polarization transfer between the pentacene excited triplet and the trityl radical but do not observe the same for the BDPA and TEMPO derivatives. The polarization transfer behavior in the pentacene-trityl system is also investigated in different glassy matrices and is found to depend markedly on the solvent used. The EPR results are rationalized with the help of femtosecond and nanosecond transient absorption measurements, yielding complementary information on the excited-state dynamics of the three pentacene derivatives. Notably, we observe a 2 orders of magnitude difference in the time scale of triplet formation between the pentacene-trityl system and the pentacene systems tethered with the BDPA and TEMPO radicals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpca.0c03498DOI Listing
July 2020

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

Am Heart J 2020 07 25;225:69-77. Epub 2020 Mar 25.

University Teaching Hospital of Kigali, Rwanda.

Background: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need.

Methods: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm, left atrial spontaneous echo-contrast or thrombus, or a CHADSVASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD.

Conclusion: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ahj.2020.03.018DOI Listing
July 2020

Rheumatic heart disease: current status of diagnosis and therapy.

Cardiovasc Diagn Ther 2020 Apr;10(2):305-315

Division of Paediatric Cardiology, Department of Paediatrics, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa.

Rheumatic heart disease (RHD) is the only preventable cardiovascular disease which causes significant morbidity and mortality particularly in low- and middle-income countries. Early clinical diagnosis is key, the updated Jones criteria increases the likelihood of diagnosis in endemic settings, including the echo diagnosis of sub-clinical carditis, polyarthralgia and monoarthritis as well as amended thresholds of minor criteria. The mainstay of rheumatic heart valve disease (RHVD) is a thorough clinical and echocardiographic investigation while severe disease is managed with medical, interventional and surgical treatment. In this report we detail some of the more recent epidemiological findings and focus on the diagnostic and interventional elements of the specific valve lesions. Finally, we discuss some of the recent efforts to improve medical and surgical management for this disease. As we are already more than a year from the historic 2018 World Heart Organization Resolution against Rheumatic Fever and Rheumatic Heart Disease, we advocate strongly for renewed efforts to prioritize this disease across the endemic regions of the world.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/cdt.2019.10.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225445PMC
April 2020

Tracking the impact of interventions against COVID-19 in absence of extensive testing.

Indian J Med Res 2020 Feb & Mar;151(2 & 3):114-115

Department of Cardiology, All India Institute of Medical Sciences, New Delhi 110 029, India.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijmr.IJMR_864_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366535PMC
May 2020

Percutaneous mitral commissurotomy versus surgical commissurotomy for rheumatic mitral stenosis: a systematic review and meta-analysis of randomised controlled trials.

Heart 2020 07 23;106(14):1094-1101. Epub 2020 Jan 23.

Cardiology, All India Institute of Medical Sciences, New Delhi, India

Aim: Patients with severe mitral stenosis (MS) and their clinicians typically choose percutaneous transvenous mitral commissurotomy (PTMC) over surgical commissurotomy (SC). However, the durability of PTMC relative to SC is uncertain. We compared the efficacy, safety and durability of PTMC with SC for the treatment of MS.

Methods: We searched EMBASE, MEDLINE and WHO ICTRP registers for randomised controlled trials (RCTs) comparing PTMC, and open and/or closed mitral commissurotomy. The principal outcomes were rate of re-intervention and symptomatic improvement as inferred from the surrogate measures of immediate postprocedural mitral valve area (MVA), MVA at ≥6 month follow-up, incidence of mitral regurgitation (MR) and restenosis. We calculated weighted mean differences (WMD) for continuous outcomes, relative risks (RR) for binary outcomes and pooled outcomes using random-effects models and assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Results: Seven RCTs with 553 patients proved eligible. Pooled estimates showed no convincing difference in the risk of restenosis or re-intervention (15/100 fewer with PTMC, 95% CI (-20 to +8); quality of evidence: moderate) or in symptoms as inferred from immediate MVA (WMD 0.15, 95% CI (-0.18 to 0.48): very low), from the incidence of postprocedural severe MR (3/100 more with PTMC, 95% CI (-1 to +10): moderate) or from MVA at 30 months.

Conclusion: Until data demonstrating convincing superiority of SC over PTMC become available, our results support the current practice of recommending PTMC to young patients with MS and favourable valve morphology, as it is associated with lower peri-procedural morbidity.

Prospero Registration Number: PROSPERO 2017 (CRD42017079512).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2019-315906DOI Listing
July 2020
-->