Utility of 68Ga-DOTANOC PET/CT in therapeutic monitoring of cardiac sarcoidosis.

Cardiac sarcoidosis usually occurs as a manifestation of systemic sarcoidosis, even though isolated cardiac involvement is not uncommon. The usefulness of 68Ga-DOTANOC PET/CT in the diagnosis of CS has been previously documented in the literature. We present a case of cardiac sarcoidosis, where 68Ga-DOTANOC PET/CT was used for monitoring response to therapy.

Imaging of cardiac sympathetic dysfunction with 18F-FDOPA PET/CT in patients with heart failure: a pilot study.

BACKGROUND: Routine use of cardiac sympathetic imaging in HF has been limited by the lower availability/sensitivity of radiotracers. This study was aimed to assess the feasibility of 18F-FDOPA (commonly available PET-radiotracer) in assessment of cardiac autonomic dysfunction. METHODS: Twenty-four controls (46.5 ± 11.1 years, 16men) and 24 patients (43.5 ± 11.0 years, 18men) with diagnosed HF (Framingham-Criteria) underwent cardiac-PET/CT. Region(s) Of Interest were drawn over entire left ventricular myocardium (LV), individual walls, and mediastinum (M). Coefficient of Variation (CV) was calculated from individual wall counts. RESULTS: HF patients had significantly lower myocardial 18F-FDOPA uptake (P < .001, independent t test) than controls [32.4% ± 9.5% global reduction; highest in apex (39.9% ± 7.0%)]. A cut-off of LV/M ≤ 1.68 could differentiate patients from controls with sensitivity and specificity of 100% and 95.8%, respectively. LV/M correlated positively with EF (Pearson coefficient = 0.460, P .031). During follow-up, 3 patients were lost to follow-up, 4 died (survival-20.5 ± 4 months), 2 worsened, and 15 remained stable/showed mild improvement. Patients who worsened/died during follow-up had higher CV than those with stable/improving symptoms [0.16 ± 0.05 vs 0.11 ± 0.05, P value .069 (independent t test); Cox regression P = .084]. CONCLUSION: Myocardial 18F-FDOPA uptake in patients with HF is significantly reduced. Higher reduction is seen in those with lower EF. CV, a maker of regional heterogeneity, is a potential prognostic marker.

A Domain-Shift Invariant CNN Framework for Cardiac MRI Segmentation Across Unseen Domains.

The emergence of various deep learning approaches in diagnostic medical image segmentation has made machines capable of accomplishing human-level accuracy. However, the generalizability of these architectures across patients from different countries, Magnetic Resonance Imaging (MRI) scans from distinct vendors, and varying imaging conditions remains questionable. In this work, we propose a translatable deep learning framework for diagnostic segmentation of cine MRI scans. This study aims to render the available SOTA (state-of-the-art) architectures domain-shift invariant by utilizing the heterogeneity of multi-sequence cardiac MRI. To develop and test our approach, we curated a diverse group of public datasets and a dataset obtained from private source. We evaluated 3 SOTA CNN (Convolution neural network) architectures i.e., U-Net, Attention-U-Net, and Attention-Res-U-Net. These architectures were first trained on a combination of three different cardiac MRI sequences. Next, we examined the M&M (multi-center & mutli-vendor) challenge dataset to investigate the effect of different training sets on translatability. The U-Net architecture, trained on the multi-sequence dataset, proved to be the most generalizable across multiple datasets during validation on unseen domains. This model attained mean dice scores of 0.81, 0.85, and 0.83 for myocardial wall segmentation after testing on unseen MyoPS (Myocardial Pathology Segmentation) 2020 dataset, AIIMS (All India Institute of Medical Sciences) dataset and M&M dataset, respectively. Our framework achieved Pearson's correlation values of 0.98, 0.99, and 0.95 between the observed and predicted parameters of end diastole volume, end systole volume, and ejection fraction, respectively, on the unseen Indian population dataset.

An unusual case of Shone's complex in an adult depicted on computed tomography angiography.

We present a case of a 22-year-old male with dyspnea on exertion where computed tomography revealed complete Shone's complex. This case highlights the complementary role of computed tomography in the anatomical evaluation of patients with complex heart diseases.

Loss of function mutation in the P2X7, a ligand-gated ion channel gene associated with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited heart failure condition, mostly found to have genetic abnormalities, and is a leading cause of sudden death in young adults. Whole exome sequencing should be given consideration as a molecular diagnostic tool to identify disease-causing mutation/s. In this study, a HCM family with multiple affected members having history of sudden death were subjected to exome sequencing along with unaffected members. Quality passed variants obtained were filtered for rarity (MAF > 0.5%), evolutionary conservation, pathogenic prediction, and segregation in affected members after removing shared variants present in unaffected members. Only one non-synonymous mutation (p. Glu186Lys or E186K) in exon 6 of P2X7 gene segregated in HCM-affected individuals which was absent in unaffected family members and 100 clinically evaluated controls. The site of the mutation is highly conserved and led to complete loss of function which is in close vicinity to ATP-binding site-forming residues, affecting ATP binding, channel gating, or both. Mutations in candidate genes which were not segregated define clinical heterogeneity within affected members. P2X7 gene is highly expressed in the heart and shows direct interaction with major candidate genes for HCM. Our results reveal a significant putative HCM causative gene, P2X7, for the first time and show that germ-line mutations in P2X7 may cause a defective phenotype, suggesting purinergic receptor involvement in heart failure mediated through arrhythmias which need further investigations to be targeted for therapeutic interventions.

Beneficial effects of fenofibrate in pulmonary hypertension in rats.

Pulmonary hypertension (PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats. FF, because of its pleiotropic property, could be helpful in reducing inflammation, oxidative stress, and reactive oxygen species. On day 1, MCT (50 mg/kg, s.c.) was given to all the rats in MCT, sildenafil, and FF group except normal control rats. After 3 days of giving MCT, sildenafil (175 µg/kg, orally) and FF (120 mg/kg, orally) were given for 25 days. Echocardiography, hemodynamic parameters, fulton's index, histopathology, oxidative stress parameters, inflammatory markers, Bcl2/Bax gene expression ratio in the right ventricle, and protein expression for NOX-1 in lungs were studied in all the groups. FF has shown to prevent decrease in ratio of pulmonary artery acceleration time to ejection time, increase in ratio of right ventricular outflow tract dimension to aortic outflow dimension, rise in right ventricular systolic pressure, right ventricular hypertrophy, increase in the percentage medial wall thickness (%MWT), increase in oxidative stress and inflammation, increase in NADPH oxidase-1 (NOX-1) expression, and decrease in mRNA expression of Bcl2/Bax ratio caused by MCT. To conclude, FF prevented MCT-induced PH in rats by various mechanisms. It might be helpful in preventing PH in patients who are likely to develop PH.

Mitral Valve Replacement Using Carpentier-Edwards Pericardial Bioprosthesis in Patients With Rheumatic Heart Disease Aged Below 40 Years: 17-Year Results.

BACKGROUND: This study was designed to evaluate patients aged less than 40 years implanted with tissue heart valves with respect to survival, thromboembolism, structural degeneration and quality of life. METHODS: Between January, 2000 and December, 2016, 132 patients (51 males) with rheumatic heart disease underwent mitral valve replacement using Carpentier-Edwards, perimount, pericardial bioprostheses. The patients' ages ranged between 12 and 39 years (mean±SD 30.12±5.51 years). RESULTS: The hospital and late mortality were 1.5% and 1.5% respectively. The total cumulative follow-up period was 1330.98 patient-years with a mean of 124.78±50.3 months (range, 1-204 months). The actuarial survival and actuarial event-free survival at 204 months was 96.9% (±0.01%) and 93.4%(±0.03%) respectively. There was one episode of thromboembolism (0.32 events per 100 patient years). Six (4.7%) patients underwent redo mitral valve replacement for severe bioprosthetic degeneration with stiffening and calcification using a Medtronic mechanical prosthesis (Medtronic Open Pivot, MN, USA). CONCLUSIONS: We conclude that Carpentier-Edwards perimount pericardial prosthesis provides satisfactory clinical performance in a young population with a low risk of degeneration and other valve-related events.

Late effects of treatment in survivors of childhood cancers: A single-centre experience.

BACKGROUND & OBJECTIVES: With improved survival of childhood cancer patients, the number of long-term cancer survivors is increasing. Some studies have assessed the long-term morbidity after childhood cancer treatment in the developing countries. This study was conducted to assess the spectrum of late effects of cancer treatment in paediatric cancer survivors. METHODS: Evaluation of the first 300 patients who completed five years of follow up in the after treatment completion clinic was done. Details of primary diagnosis, treatment received and current clinical status were noted. The spectrum of late effects was ascertained by appropriate investigations. RESULTS: Haematological malignancies comprised 25 per cent of total cases. Most common primary diagnosis comprised acute lymphoblastic leukaemia, retinoblastoma and Hodgkin's lymphoma. The median age at evaluation and follow up was 14 and 8.5 yr, respectively. Twenty three per cent (69) of the survivors had a minimal disability (growth retardation or underweight), 13 per cent (39) had moderate disabilities needing medical attention (hepatitis B surface antigen positive, myocardial dysfunction, azoospermia and hypothyroidism), while two per cent had major/life-threatening disabilities (mental retardation, liver disease and mortality). Eleven patients relapsed on follow up, of those five patients expired. Two second malignancies were recorded during the period of follow up. INTERPRETATION & CONCLUSIONS: Late effects were of concern; however, severe disability (Grade 3-5) was seen in only two per cent survivors. Lifelong follow up of childhood cancer survivors is required to assess cancer-related morbidity, occurrence of a secondary neoplasm, to facilitate timely diagnosis and to implement remedial or preventive interventions to optimize health outcomes. Awareness towards the existence of late effects of cancer therapy is required among parents, patients and health professionals.

Low holo-transcobalamin levels are prevalent in vegetarians and is associated with coronary artery disease in Indian population.

Coronary artery disease (CAD) has been increasing alarmingly in India. We had earlier shown that vitamin B12 deficiency is associated with CAD in Indian population. However, only about a quarter of the total vitamin B12 is internalised in the cells by the proteins transcobalamin II. Vitamin B12-bound transcobalamin II (holotranscobalamin, holoTC) is thus referred to as biologically active B12. In this study, we ascertained the levels of holoTC in 501 CAD cases and 1253 healthy controls and for the first time show that holoTC levels are significantly lower (p = 2.57E-4) in CAD (26.81 pmol/l) cases as compared to controls (29.97 pmol/l).

Next generation sequencing in cardiomyopathy: towards personalized genomics and medicine.

Next generation sequencing (NGS) is perhaps one of the most exciting advances in the field of life sciences and biomedical research in the last decade. With the availability of massive parallel sequencing, human DNA blueprint can be decoded to explore the hidden information with reduced time and cost. This technology has been used to understand the genetic aspects of various diseases including cardiomyopathies. Mutations for different cardiomyopathies have been identified and cataloging mutations on phenotypic basis are underway and are expected to lead to new discoveries that may translate to novel diagnostic, prognostic and therapeutic targets. With ease in handling NGS, cost effectiveness and fast data output, NGS is now considered as a diagnostic tool for cardiomyopathy by providing targeted gene sequencing. In addition to the number of genetic variants that are identified in cardiomyopathies, there is a need of quicker and easy way to screen multiple genes associated with the disease. In this review, an attempt has been made to explain the NGS technology, methods and applications in cardiomyopathies and their perspective in clinical practice and challenges which are to be addressed.

Pharmacogenomic biomarkers in coronary artery disease: a narrative review.

Coronary artery disease (CAD) has a high mortality rate. Despite various therapeutic targets, non-responsiveness to drugs remains a prevalent issue. Pharmacogenomics assesses the way an individual's genetic attributes affect their likely response to drug therapy. Single-nucleotide polymorphisms play a crucial role in determining these outcomes. This review offers an overview of single-nucleotide polymorphisms investigated in clinical studies and their associations with drug response/nonresponse in the treatment of CAD. A total of 104 studies of whole sets of chromosomes and several genes were explored. A total of 161 polymorphisms exhibited associations with drug response/nonresponse in CAD across diverse ethnic populations. This pool can serve as a pharmacogenomic biomarker for predicting response to drug therapy in patients with CAD.

Profile of patients referred for lung transplant and their transplant-free survival.

INTRODUCTION: Lung transplant (LTx) is a potential treatment option for all patients with chronic, end-stage respiratory disease, who are refractory to optimal medical therapy or where no medical therapy exists. In India, LTx is still in its evolving stages and published literature is sparse. The current study was carried out to study the selection criteria for lung transplant and to evaluate the clinical and socio-economic profile of patients referred for the same at a tertiary health care facility. METHODS: The study was a descriptive, prospective, observational study. All adults referred for lung transplant were evaluated for clinical and laboratory profiles. All enrolled patients were assessed for presence of referral criteria, listing criteria, contraindications, and willingness for lung transplant. These patients were followed up for 2 years for transplant-free survival, and the Cox proportional hazards model was used to determine independent predictors of all-cause mortality. RESULTS: A total of 103 were included in study. The most common diagnosis was interstitial lung disease (57.2%), followed by bronchiectasis (17.5%) and COPD (13.6%). Most patients were referred for LTx at an advanced stage as 90% met listing criteria. Fifty-four (52.4%) patients had an absolute or relative contraindication to transplant; however, the majority of those contraindications were modifiable. Patients with a lower socio-economic status were less likely to be willing for LTx. The median survival was 757 days. A 6-minute walk distance (6MWD) lesser than 250 m was found to be an independent predictor of mortality. CONCLUSION: Making patients aware about lung transplant early in their treatment may give them sufficient time to come to terms with their disease and understand the risk and benefits associated. Efforts should be focused on screening and early treatment of reversible contraindications for the eligible patients. Patients with 6MWD < 250 m are at increased risk of mortality.

Quantitative assessment of cardiac mechanical synchrony using equilibrium radionuclide angiography.

BACKGROUND: Data on normal parameters of cardiac mechanical synchrony is limited, variable and obtained from small cohorts till date. In most studies, software used for such assessment has not been mentioned. The aim of study is to establish normal values of mechanical synchrony with equilibrium radionuclide angiography (ERNA) in a larger population using commercially available software. METHODS: We retrospectively analysed ERNA studies of 108 patients having low pretest likelihood of coronary artery disease, no known history of cardiac disease, normal electrocardiogram and whose ERNA studies were considered normal by experienced observers. In addition, ten patients diagnosed with dilated cardiomyopathy (DCM) and having LVEF ≤ 40% underwent ERNA. Fourier first harmonic analysis of phase images was used to quantify synchrony parameters using commercially available software (XT-ERNA). Intraventricular synchrony for each ventricle was measured as the standard deviation of the LV and RV mean phase angles (SD LVmPA and SD RVmPA, respectively). Interventricular synchrony was measured as LV-RVmPA. Absolute interventricular delay was calculated as absolute difference between LV and RVmPA (without considering ± sign). All variables were expressed in milliseconds (ms) and degree (°). Intra-observer and inter-observer variabilities were assessed. Cut-off values for parameters were calculated from the normal database, and validated against patient group. RESULTS: On phase analysis, LVmPA was observed to be 343 ± 48.5 milliseconds (174.7° ± 18.5°), SD LVmPA was 16.3 ± 5.4 milliseconds (8.2° ± 2.5°), RVmPA was 339 ± 50.4 milliseconds (171.8° ± 18.5°) and SD RVmPA was 37.3 ± 15.7 milliseconds (18.7° ± 7.2°). LV-RVmPA was observed to be 3.9 ± 21.7 milliseconds (2.9° ± 9.6°) and absolute interventricular delay was 16.3 ± 14.8 milliseconds (7.9° ± 6.1°). The cut-off values for the presence of dyssynchrony were estimated as SD LVmPA > 27.1 milliseconds (>13.2°), SD RVmPA > 68.7 milliseconds (>33.1°) and LV-RVmPA > 47.3 milliseconds (>22.1°). There was no statistically significant intra-observer or inter-observer variability. Using these cut offs, 9 patients with DCM showed the presence of left intraventricular dyssynchrony, 5 had right intraventricular dyssynchrony and 2 had interventricular dyssynchrony. CONCLUSIONS: ERNA phase analysis offers an objective and reproducible tool to quantify cardiac mechanical synchrony using commercially available software and can be used in routine clinical practice to assess mechanical dyssynchrony.

Inflammatory markers are elevated in Eisenmenger syndrome.

Inflammation may be an important contributing factor to the progression of Eisenmenger syndrome (ES). Markers of systemic inflammation in ES have not been systematically studied. Inflammatory markers including high-sensitivity C-reactive protein (hs-CRP), interleukin-2 (IL-2), IL-6, and interferon-γ (IFN-γ) were measured in 42 consecutive ES patients (mean age, 24.3 ± 10.6 years) compared with their levels in 22 healthy control subjects. The patients were followed up for a mean duration of 16.3 ± 13.7 months. The levels of inflammatory markers were correlated with clinical and hemodynamic variables at baseline and the outcomes of death, hospitalization, and worsening World Health Organization (WHO) functional class at follow-up evaluation. Compared with the control subjects, ES patients showed a significant elevation in hs-CRP (2.99 ± 3.5 vs 1.1 ± 0.9 mg/dl; p = 0.002) and IFN-γ (41.3 ± 43.6 vs 10.4 ± 6.9 pg/ml; p < 0.001) levels. The levels of IL-2 and IL-6 also were elevated but did not differ significantly from those in the control subjects. The patients with hs-CRP levels higher than 3 mg/dl were significantly older (28.9 ± 10.6 vs 21.5 ± 9.8 years) and had a significantly shorter 6-min walk distance (421.5 ± 133.2 vs 493.3 ± 74.8 m). The levels of inflammatory markers did not correlate with baseline parameters or clinical outcomes. To conclude, the levels of hs-CRP and IFN-γ are significantly elevated in ES. Elevated hs-CRP in ES was associated with older age and shorter 6-min walk distance, but the levels of inflammatory markers were not predictive of clinical events.

Imaging Acute Myocarditis with 68Ga-DOTANOC PET/CT.

Somatostatin receptor (SSTR) imaging is a useful method in the diagnosis of acute myocarditis. We present a case of a 54-year-old male with a clinical diagnosis of acute myocarditis in whom, 68Ga-DOTANOC positron emission tomography/computed tomography PET/CT showed diffuse left ventricular myocardial uptake. SSTR imaging can act as a surrogate marker of active inflammation. SSTR imaging is useful in deciding site of biopsy, assessing response to therapy and for prognostication.

Posttransplant lymphoproliferative disorder in a heart transplant recipient: a case report.

Malignancy in heart transplant recipients is a grave complication. Post-transplant lymphoproliferative disorder (PTLD) is the second most common tumour in adults and commonest in children. The incidence varies with the transplanted organ from 1 to 2% following kidney transplantation to as high as 10% following thoracic organ transplantation due to different immunosuppression intensity. PTLD include a wide spectrum of diseases ranging from benign proliferation of lymphoid tissue to frank malignancy with aggressive behaviour (lymphoma). Epstein-Barr virus (EBV) infection and prolonged immunosuppressant therapy are implicated in the pathogenesis of PTLD. The incidence of PTLD varies from 2.6% at 1 year to 28% at 10 years post-transplant. Seronegativity for EBV in recipients with seropositive donors increases the risk of PTLD in recipients. The majority of early-onset PTLDs (85%) are of B-cell origin and associated with EBV. Timely and accurate diagnosis with histological examination of lymphoid tissue is essential for early intervention. Reduction of immunosuppressive therapy (IST) and rituximab usually are effective in remission of PTLD. In resistant cases, chemotherapy is given with or without rituximab. Adoptive T-cell transfer represents a promising therapeutic approach. Early PTLD respond well to lowering immunosuppression and has a favourable prognosis compared to late PTLD. Five-year survival is 30% for high-grade lymphomas. The prognosis of EBV-negative lymphomas is worse. One out of 40 heart transplant recipients followed up in our centre developed PTLD. He was treated to remission and we describe this case here.