A proposed strategy for management of immunosuppression in heart transplant patients with COVID-19

There is limited experience in management of orthotopic heart transplant (OHT) patients with COVID-19. In this study, we present our initial experience using a standardized management algorithm. Data collection was performed on OHT patients with COVID-19 after March 10, 2020 (declaration of state of emergency in Massachusetts). Among the 358 OHT patients currently followed at our program, 5 patients (1.4%) tested positive for COVID-19 (median age 50 years [IQR, 49-58], duration post-OHT 21 years [IQR, 6-25], and 4 of 5 [80%] were men). Among the 5 OHT patients, 2 of 5 (20%) had mild disease and had no change in baseline immunosuppression therapy. Two of 5 (20%) had moderate disease and received remdesivir as part of a clinical trial and reduced immunosuppression therapy. One patient (20%) died prior to presenting to the hospital, consistent with 20% case fatality rate. Four patients (80%) are doing well 4 weeks post-discharge. In this small cohort of OHT patients with COVID-19, we report a 1.4% COVID-19 infection rate and 20% case fatality rate. All OHT patients managed under our clinical management algorithm had good short-term outcomes. Further study to estimate the true risk profile of OHT patients and validate the proposed management strategy is warranted.     

Termination of ventricular tachycardia with bursts of rapid ventricular pacing

Bursts of rapid ventricular pacing used during 573 episodes of ventricular tachycardia in 23 patients terminated 5 12 episodes (89 percent), with burst rates averaging 56 beats/min above the ventricular tachycardia rate, for 5 to 10 captures. Tachycardia was accelerated by pacing bursts to rates below 300 beats/min in 16 episodes (3 percent); 10 of these terminated spontaneously or responded to further bursts. Acceleration of heart rate to more than 300 beats/min or ventricular fibrillation occurred six times (1 percent), each episode requiring direct current cardioversion. Pacing bursts had no effect in 38 instances (7 percent), mostly in patients with terminal cardiogenic shock. Implantable pacemakers delivering bursts of rapid ventricular pacing were placed in two patients who have used these units at home. No deaths were associated with bursts of rapid ventricular pacing, which is an effective, rapid, pleasant alternative to repeated direct current cardioversion and a useful tool during electrophysiologic testing in patients with recurrent tachycardia.     

Utility of impedance cardiography for the identification of short-term risk of clinical decompensation in stable patients with chronic heart failure.

OBJECTIVES: This study sought to assess the potential utility of impedance cardiography (ICG) in predicting clinical deterioration in ambulatory patients with heart failure (HF). BACKGROUND: Impedance cardiography uses changes in thoracic electrical impedance to estimate hemodynamic variables, but its ability to predict clinical events has not been evaluated. METHODS: We prospectively evaluated 212 stable patients with HF and a recent episode of clinical decompensation who underwent serial clinical evaluation and blinded ICG testing every 2 weeks for 26 weeks and were followed up for the occurrence of death or worsening HF requiring hospitalization or emergent care. RESULTS: During the study, 59 patients experienced 104 episodes of decompensated HF (16 deaths, 78 hospitalizations, and 10 emergency visits). Multivariate analysis identified 6 clinical and ICG variables that independently predicted an event within 14 days of assessment. These included three clinical variables (visual analog score, New York Heart Association functional class, and systolic blood pressure) and three ICG parameters (velocity index, thoracic fluid content index, and left ventricular ejection time). The three ICG parameters combined into a composite score was a powerful predictor of an event during the next 14 days (p = 0.0002). Visits with a high-risk composite score had 2.5 times greater likelihood and those with a low-risk score had a 70% lower likelihood of a near-term event compared with visits at intermediate risk. CONCLUSIONS: These results suggest that when performed at regular intervals in stable patients with HF with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation.     

Human Stimulus Factor Is a Promising Peptide for Delivery of Therapeutics

Fluticasone propionate uptake in the presence of a proprietary cell-penetrating peptide (human stimulus factor, [HSF]) based on the N-terminal domain of lactoferrin was studied, alone and in combination with salmeterol, using an air interface Calu-3 epithelial model. The HSF enhanced uptake and transport of fluticasone propionate across the epithelial barrier when alone and in presence of salmeterol. This was attributed to transcellular-mediated uptake. This HSF is a promising peptide for delivery of therapeutics where enhanced epithelial penetrating is required.     

Clinical relevance of major histocompatibility complex class I chain–related molecule A (MICA) antibodies in live donor renal transplantation – Indian Experience

Antibody-mediated rejections (AMR) in the absence of circulating anti-HLA-DSA have highlighted the role of non-HLA antibodies, particularly those directed against endothelial cells. Of these, MICA (major histocompatibility complex class I chain–related molecule A) antibodies are the most notable and important because of their potential in promoting graft rejections. Limited studies have focused on the impact of MICA donor-specific antibodies (DSA) on graft outcome as compared to those that are not donor-specific (NDSA). We evaluated pre- and post-transplant sera at POD 7, 30, 90, 180 and the time of biopsy from 206 consecutive primary live donor renal transplant recipients for anti-MICA and anti-HLA antibodies using single antigen bead assay on a Luminex platform. Recipients who developed MICA antibodies and their donors were phenotyped for MICA alleles. For the purpose of antibody analysis, patients were categorized into three major groups: biopsy-proven AMR, acute cellular rejection (ACR) and those with no rejection episodes (NRE). During the mean follow-up period of 17.37 ± 6.88 months, 16 of the 206 recipients developed AMR, while ACR was observed in only 13 cases. A quarter (25%) of the AMR cases had anti-MICA antibodies as compared to 7.7% of those experiencing ACR and 6.2% of the NRE group. Allelic typing revealed that all MICA Ab +ve AMR cases were due to the presence of donor-specific antibodies. MICA-DSA even in the absence of HLA-DSA was significantly associated with AMR but not with ACR when compared with the NRE group (P = <.01).