A Novel Heart Failure Diagnostic Risk Score Using a Minimally Invasive Subcutaneous Insertable Cardiac Monitor.

BACKGROUND: The authors tested the hypothesis that physiological information from sensors within a minimally invasive, subcutaneous, insertable cardiac monitor (ICM) could be used to develop an ambulatory heart failure risk score (HFRS) to accurately identify heart failure (HF) patients, across the ejection fraction spectrum, at high risk of an impending worsening heart failure event (HFE). OBJECTIVES: The purpose of this study was to examine performance of ICM-based, multiparameter, dynamic HFRS to predict HFEs in patients with NYHA functional class II/III HF. METHODS: In 2 observational cohorts, HF patients were implanted with an ICM; subcutaneous impedance, respiratory rate, heart rate and variability, atrial fibrillation burden, ventricular rate during atrial fibrillation, and activity duration were combined into an HFRS to identify the probability of HFE within 30 days. Patients and providers were blinded to the data. HFRS sensitivity and unexplained detection rate were defined in 2 independent patient population data sets. HFEs were defined as hospitalization, observation unit, or emergency department visit with a primary diagnosis of HF, and intravenous diuretic treatment. RESULTS: First data set (development): 42 patients had 19 HFE; second data set (validation): 94 patients had 19 HFE (mean age 66 ± 11 years, 63% men, 50% with LVEF ≥40%, 80% NYHA functional class III). Using a high-risk threshold = 7.5%, development and validation data sets: sensitivity was 73.7% and 68.4%; unexplained detection rate of 1.4 and 1.5 per patient-year; median 47 and 64 days early warning before HFE. CONCLUSIONS: ICM-HFRS provides a multiparameter, integrated diagnostic method with the ability to identify when HF patients are at increased risk of heart failure events. (Reveal LINQ Evaluation of Fluid [REEF]; NCT02275923, Reveal LINQ Heart Failure [LINQ HF]; NCT02758301, Algorithm Using LINQ Sensors for Evaluation and Treatment of Heart Failure [ALLEVIATE-HF]; NCT04452149).

Identifying Challenges and Potential Solutions for Sustainable Kidney Nutrition Care Delivery in Selected Asian Countries.

BACKGROUND: Recent surveys highlight gross workforce shortage of dietitians in global kidney health and significant gaps in renal nutrition care, with disparities greater in low/low-middle income countries. OBJECTIVE: This paper narrates ground experiences gained through the Palm Tocotrienols in Chronic Hemodialysis (PaTCH) project on kidney nutrition care scenarios and some Asian low-to-middle-income countries namely Bangladesh, India, and Malaysia. METHOD: Core PaTCH investigators from 3 universities (USA and Malaysia) were supported by their postgraduate students (n = 17) with capacity skills in kidney nutrition care methodology and processes. This core team, in turn, built capacity for partnering hospitals as countries differed in their ability to deliver dietitian-related activities for dialysis patients. RESULTS: We performed a structural component analyses of PaTCH affiliated and nonaffiliated (Myanmar and Indonesia) countries to identify challenges to kidney nutrition care. Deficits in patient-centered care, empowerment processes and moderating factors to nutrition care optimization characterized country comparisons. Underscoring these factors were some countries lacked trained dietitians whilst for others generalist dietitians or nonclinical nutritionists were providing patient care. Resolution of some challenges in low-to-middle-income countries through coalition networking to facilitate interprofessional collaboration and task sharing is described. CONCLUSIONS: We perceive interprofessional collaboration is the way forward to fill gaps in essential dietitian services and regional-based institutional coalitions will facilitate culture-sensitive capacity in building skills. For the long-term an advanced renal nutrition course such as the Global Renal Internet Course for Dietitians is vital to facilitate sustainable kidney nutrition care.

COMPETENCE Trial: The EVAHEART 2 continuous flow left ventricular assist device.

BACKGROUND: Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. METHODS: A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. RESULTS: The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. CONCLUSIONS: The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3.

A Narrative Review COVID-19 in Solid-Organ Transplantation: Real-World Evidence From India.

Worldwide, India ranks number 2 and 3 for COVID-19 burden and absolute transplant numbers, respectively. Here, we summarized our single and multicenter Indian studies on solid-organ transplant during the COVID-19 pandemic. During the pandemic, solid-organ transplants declined 40% to 50%. The mortality rate in COVID-19-positive kidney transplant recipients (11.6%) was lower in India compared with the developed world during the first wave and lower compared with maintenance hemodialysis patients (13% to 38%) but significantly higher compared with the nonimmunosuppressed general population (1% to 3%) in India. We contributed to National Organ and Tissue Transplant Organization transplant-related guidelines to increase safety and access to solid-organ transplant. We reported the safety and feasibility of remdesivir (n = 57) and convalescent plasma therapy (n = 10) in kidney transplant recipients. We reported 100% patient and graft survival without any complications related to COVID-19 in a large cohort of kidney transplant recipients who recovered from COVID-19 (n = 372) and a large cohort of kidney transplant recipients of living donors (n = 31) who recovered from COVID-19 without any change in induction and maintenance immunosuppression. COVID-19 disease severity and mortality in the second episode (reoccurring infection) was higher (46%) compared with the first episode (11.6%). There was 4.4% incidence of COVID-19-associated mucormycosis in kidney transplant recipients with mortality of 46% in the second wave. We reported COVID-19 vaccine safety with suboptimal efficacy in kidney transplant recipients and dialysis patients compared with the general population. Our report suggested that transplant with carefully selected COVID-19-recovered donors and patients may be feasible and safe, at least over the short term. Continued research is needed on vaccine efficacy, booster doses, and long-term follow up sequelae.

One-Year Outcomes with Use of Anti-T-Lymphocyte Globulin in Patients Undergoing Kidney Transplantation: Results from a Prospective, Multicentric, Observational Study from India.

INTRODUCTION: Large-scale Indian data on the use of anti-T-lymphocyte globulin (ATLG) (Grafalon®) as induction therapy in kidney transplantation (KT) patients is lacking. The aim of this study was to determine the 1-year patient and graft survival outcomes with the use of ATLG as induction regimen in KT. METHODS: In a prospective, multicentric, observational study, adult patients who underwent ABO-compatible KT and had received ATLG as a part of induction were included in the study. The primary outcome measure was overall survival and death-censored graft survival at 12 months. The primary safety outcome was assessed by development of infectious complications and graft rejection. RESULTS: In total, 359 patients were included in this study. The mean age was 42.77 ± 12.30 years and 83% were male. The average ATLG dose per patient was 6.2 ± 2.2 mg/kg whereas average cumulative dose per patient was 389.6 ± 149.8 mg. The rate of graft dysfunction was 13.4% of patients and 6.7% had biopsy-proven acute rejection (BPAR). There were a total of 12 (3.3%) deaths and one graft loss. Overall survival and death-censored graft survival at 12 months were 96.65% and 99.44%, respectively. The rate of infections was 13.6% with urinary tract infections being most common. CONCLUSION: ATLG at an average dose of 6 mg/kg is an effective and safe induction regimen immunosuppressant for ABO-compatible KT with favourable impact on survival and graft function in Indian patients.

Management strategies and outcomes in renal transplant recipients recovering from COVID-19: A retrospective, multicentre, cohort study.

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

Tacrolimus-induced acute pancreatitis and diabetic ketoacidosis (DKA) in pediatric kidney transplant recipient.

BACKGROUND: Calcineurin inhibitors (CNIs) are often associated with abnormalities in glucose and lipid metabolism. Tacrolimus is the most potent CNI which is nowadays used almost universally as a part of triple-drug immunosuppression after kidney transplantation. Tacrolimus can cause islet cell damage and decrease in insulin secretion which can lead to post-transplant diabetes mellitus and rarely diabetic ketoacidosis. Although rare, acute pancreatitis has also been implicated by a few case reports to be associated with tacrolimus. However, tacrolimus-induced acute pancreatitis has not been reported in pediatric kidney transplant recipient till date. CASE DESCRIPTION: We report the first case of tacrolimus-induced acute pancreatitis in association with hypertriglyceridemia and DKA in a child early after kidney transplant. The patient was managed with supportive treatment, and tacrolimus was stopped for three days and then switched to cyclosporine-based regimen. The patient became euglycemic within 8 weeks of switching to cyclosporine and did not have any recurrence of pancreatitis. CONCLUSION: Tacrolimus-induced pancreatitis is rare in the setting of kidney transplants and prompt diagnosis and management can lead to a successful outcome.

Current Scenarios of Pediatric Transplants of Kidney, Liver, Heart, and Lung in India: Systematic Review and Meta-Analysis.

OBJECTIVES: There is no systematic review and meta- analysis for pediatric solid-organ transplants in India. The objective of the study was to collect high-evidence data in this regard. MATERIALS AND METHODS: A systematic review and meta- analysis was performed for pediatric solid-organ transplants in India. We used the search engines of PubMed, Google Scholar, PubMed Central, Embase, and MEDLINE from beginning of data availability until April 26, 2022. Data from 2 participating centers were also used. Analyses were performed by the DerSimonian random model. RESULTS: Of 50 000 primary searches, only 31 studies were included for analysis. In total, data for pediatric kidney (n = 1057), liver (n = 914), and heart (n = 117) were reported. For the pediatric kidney, the 1-year, 5-year, and 10-year patient survival rates were 96% (range, 93%-99%; I² = 91.17%, H² = 11.33, P < .01), 90% (range, 85%-94%; I² = 93.54%, H² = 15.47, P < .01), and 75% (range, 62%-88%; I² = 97.36%, H² = 37.82, P < .01), respectively. The 1-year, 5-year, and 10-year renal graft survival rates were 93% (range, 90%-96%; I² = 63.82, H² = 2.76, P < .01), 83% (range, 76%-89%; I² = 86.39%, H² = 7.35, P < .01), and 66% (range, 57%-75%; I² = 81.68%, H² = 5.46, P < .01), respectively. The acute rejection rate was 23% (range, 20%-27%; I² = 5.44%, H² = 1.06, P = .39). For the pediatric liver transplant, the 1-year and 5-year survival rates were 92% (range, 89%-95%; I² = 49.96%, H² = 2, P < .04) and 88% (range, 85%-90%; I² = 0; H² = 1, P = .72), respectively. CONCLUSIONS: The outcomes of pediatric solid-organ transplants in India are comparable to those of the Western world. However, cause of graft loss and patient death is largely attributed to infections, unlike the experiences reported in the West. An effective registry is a primary pillar to expand pediatric solid- organ transplants in India.

Post-COVID Multisystem Inflammatory Syndrome-Adult (MIS-A) Presenting with Rhabdomyolysis and AKI.

Multisystem inflammatory syndrome is a rarely reported post-COVID (coronavirus disease) phenomenon in adults. Our understanding of the multisystem inflammatory syndrome- adult (MIS-A) is based on multiple case reports that have demonstrated heterogeneous clinical presentations and treatment options. Rhabdomyolysis is an unusual presentation of MIS-A. We report the case of a 61-year-old man who presented with rhabdomyolysis with acute kidney injury (AKI), acute inflammatory demyelinating polyneuropathy (AIDP), myocarditis, disseminated intravascular coagulation, and minimal respiratory symptoms. The patient was found to have post-COVID inflammatory syndrome and recovered with supportive treatment and intravenous immunoglobulin (2 g/kg over 5 days). COVID-19 (coronavirus disease 2019) antibody positivity played a significant role in making the diagnosis of MIS-A and in providing prompt treatment.

Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial.

BACKGROUND: Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing. OBJECTIVES: In this post hoc analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness of Medical and Invasive Approaches-Chronic Kidney Disease), we compared outcomes of patients not listed versus those listed according to management strategy. METHODS: In the ISCHEMIA-CKD trial (n = 777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction) and secondary (death, nonfatal myocardial infarction, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed. RESULTS: Compared with those not listed, listed patients were younger (60 years vs 65 years), were less likely to be of Asian race (15% vs 29%), were more likely to be on dialysis (83% vs 44%), had fewer anginal symptoms, and were more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios for the primary outcome were 0.91 (95% confidence interval [CI]: 0.54-1.54) and 1.03 (95% CI: 0.78-1.37) for those listed and not listed, respectively (pinteraction= 0.68). Adjusted hazard ratios for secondary outcomes were 0.89 (95% CI: 0.55-1.46) in listed and 1.17 (95% CI: 0.89-1.53) in those not listed (pinteraction = 0.35). CONCLUSIONS: In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant. (ISCHEMIA-Chronic Kidney Disease Trial [ISCHEMIA-CKD]; NCT01985360).

A Multicenter Cohort Study From India of 75 Kidney Transplants in Recipients Recovered After COVID-19.

BACKGROUND: There is limited current knowledge on feasibility and safety of kidney transplantation in coronavirus disease-19 (COVID-19) survivors. METHODS: We present a retrospective cohort study of 75 kidney transplants in patients who recovered from polymerase chain reaction (PCR)-confirmed COVID-19 performed across 22 transplant centers in India from July 3, 2020, to January 31, 2021. We detail demographics, clinical manifestations, immunosuppression regimen, laboratory findings, treatment, and outcomes. Patients with a previous diagnosis of COVID-19 were accepted after documenting 2 negative severe acute respiratory syndrome coronavirus 2 PCR tests, normal chest imaging with complete resolution of symptom for at least 28 d and significant social distancing for 14 d before surgery. RESULTS: Clinical severity in patients ranged from asymptomatic (n = 17, 22.7%), mild (n = 36.48%), moderate (n = 15.20%), and severe (n = 7.9.3%) disease. Median duration between PCR positive to transplant was 60 d (overall) and increased significantly from asymptomatic, mild, moderate, and severe disease (49, 57, 83, 94 d, P 0.019), respectively. All recipients and donors were asymptomatic with normal creatinine after surgery at a median (interquartile range) follow-up of 81 (56-117) d without any complications relating to surgery or COVID-19. Patient and graft survival was 100%, and acute rejection was reported in 6.6%. CONCLUSIONS: Prospective kidney transplant recipients post-COVID-19 can be considered for transplantation after comprehensive donor and recipient screening before surgery using a combination of clinical, radiologic, and laboratory criteria, careful pretransplant evaluation, and individualized risk-benefit analysis. Further large-scale prospective studies with longer follow-up will better clarify our initial findings. To date, this remains the first and the largest study of kidney transplantation in COVID-19 survivors.

Is it Safe to Be Transplanted From Living Donors Who Recovered From COVID-19? Experience of 31 Kidney Transplants in a Multicenter Cohort Study From India.

BACKGROUND: There is lack of data on feasibility and safety of kidney transplants from living donors who recovered from COVID-19. METHODS: Here, we present a retrospective cohort study of 31 kidney transplant recipients (KTR) from living donors who recovered from polymerase chain reaction confirmed COVID-19 across 19 transplant centers in India from July 3, 2020, to December 5, 2020. We detailed demographics, clinical manifestations, immunosuppression regimen, treatment, and outcomes. Donors with a previous diagnosis of COVID-19 were accepted after documenting 2 negative polymerase chain reaction tests with complete symptom resolution for at least 28 days and significant social distancing for 14 days before surgery. RESULTS: COVID-19 clinical severity in donors ranged from completely asymptomatic (71%, n = 22) to mild infection (29%, n = 9). None progressed to moderate or severe stages of the disease in the entire clinical course of home treatment. Patient and graft survival was 100%, respectively, with acute cellular rejection being reported in 6.4% (n = 2) recipient. All recipients and donors were asymptomatic with normal creatinine at median follow-up of 44 days after surgery without any complications relating to surgery and COVID-19. CONCLUSIONS: Our data support safety of proceeding with living donation for asymptomatic individuals with comprehensive donor, recipients screening before surgery, using a combination of clinical, radiologic, and laboratory criteria. It could provide new insights into the management of KTR from living donors who have recovered from COVID-19 in India. To the best of our knowledge, this remains the largest cohort of KTR from living donors who recovered from COVID-19.

Glomerular Diseases with Reference to COVID-19.

COVID pandemic affected every individual across the world. Patients with primary glomerular disease and glomerular disease secondary to systemic diseases who are on moderate to high doses of immunosuppression are at an increased risk of COVID because of their immunosuppressed state. The data to quantify the degree of risk in relation to the amount of immunosuppression or their duration of use is not robust. The patients on immunosuppression need to modify the drugs balancing the risk relapse and flare of the disease, simultaneously minimizing the risk of developing COVID. We tried to develop a guideline about the modification of the treatment regimen in such conditions.

Managing Children With Renal Diseases During the COVID-19 Pandemic.

The coronavirus outbreak is a rapidly evolving pandemic, placing unprecedented strain on health-care systems. COVID-19 presents challenges for management of children with renal diseases, especially those receiving long-term immunosuppressive medications, including renal transplant recipients and those with chronic kidney disease and acute kidney injury requiring dialysis. Our preparedness for managing this vulnerable group of children is the need of the hour. The purpose of this article is to provide guidance to caregivers and health care personnel involved in management of children with renal diseases and to ensure patient well-being, while protecting staff from infection.

Multidisciplinary Consensus Document on the Management of Uncontrolled Hypertension in India.

Cardiovascular disease is predicted to be the largest cause of death and disability in India by 2020. Hypertension (HT), one of the main contributing factors, presents a significant public health burden. Inability to achieve adequate blood pressure (BP) control results in uncontrolled hypertension (UHT). The prevalence of UHT is high in India, with only about 9-20% of patients achieving target BP goals. Presently, there are no guidelines specific to UHT, which if left uncontrolled can lead to resistant HT, chronic kidney disease and other complications of HT. A multidisciplinary panel, comprising of specialists in cardiology, nephrology and internal medicine, was convened to address the diagnosis and management of UHT in the Indian population. The panel identified key points concerning UHT and discussed management recommendations in the Indian clinical setting.

"Get a Grip on Hypertension": EXPLORING THE USE OF ISOMETRIC HANDGRIP TRAINING IN CARDIOPULMONARY REHABILITATION PATIENTS.

PURPOSE: Isometric handgrip (IHG) training lowers systolic and diastolic blood pressure (SBP and DBP, respectively), but the efficacy of IHG training in cardiopulmonary rehabilitation patients is unknown. The purpose of this study was to determine if IHG decreases blood pressure in cardiopulmonary rehabilitation patients. METHODS: Cardiopulmonary rehabilitation program participants (n = 11; 50-80 yr old) were randomized to IHG (n = 6) or control (CON; no treatment; n = 5) groups. IHG participants completed an IHG training program at 30% maximal voluntary contraction, 3 d/wk for 6 wk. Resting SBP, DBP, and heart rate were assessed weekly. RESULTS: Mean regression for SBP following IHG was negative (-1.04 ± 0.80). Mean regression in the CON group was positive (0.50 ± 0.88), but there was no significant difference between groups. Separate analysis of weeks 1 to 7 yielded a negative mean regression (-1.12 ± 0.54) in the IHG group, but positive (1.2 ± 0.60) in the CON group. A Wilcoxon test of these differences yielded significance for SBP (P = .009). In 3 of 6 IHG participants, SBP was lower (mean ± SD: -16 ± 11 mm Hg; P = .12), and in 2 IHG participants, DBP was lower (-9 ± 1 mm Hg; P = .06) compared with baseline. In 2 of 5 CON participants, SBP was not significantly lower (-11 ± 7 mm Hg) and, in 3 of 5 CON participants, DBP was lower (-7 ± 4 mm Hg; P = .04). CONCLUSIONS: Our data suggest that standard IHG training may be inadequate for blood pressure management immediately following a major cardiac or pulmonary event. Future work with a larger cohort and more developed training protocol to determine the efficacy of IHG training in patients with cardiopulmonary disease is warranted.