Background Little is known about the impact of the global coronavirus disease-2019 (COVID-19) pandemic on patients with cardiovascular disease (CVD), the biggest global killer and major risk factor for severe COVID-19 infections. We aim to explore the indirect consequences of COVID-19 on health-related quality of life (HRQoL) of patients with CVD. Methods Eighty-one adult outpatients with CVD were assessed using the EQ-5D, a generic health status instrument with five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), before and during the pandemic. Changes in the EQ-5D dimensional responses were compared categorically as well as using the dimension-specific sum-score (range 1–3, with a higher score indicating worse health). The responses and sum-score were compared using the exact test of symmetry and the paired t-test, respectively. Results These patients [mean age (SD) 59.8 (10.5); 92.6% males; 56% New York Heart Association (NYHA) functional class I] had coronary artery disease (69%), heart failure (28%), or arrhythmias (15%). None experienced change in NYHA class between assessments. About 30% and 38% of patients reported problems with at least one of the EQ-5D dimensions pre-pandemic and during the pandemic, respectively. The highest increase in health problems was reported for anxiety/depression (12.5% pre-pandemic vs 23.5% during pandemic; p = 0.035) with mean domain-specific score from 1.12 (SD 0.33) to 1.25 (SD 0.46) (standardized effect size = 0.373, p = 0.012). There was no meaningful change in other dimensions as well as overall HRQoL. Conclusion The COVID-19 pandemic is associated with a significant worsening of the mental health of patients with CVD.

Enzymatic secretion of immune cells (leukocytes) plays a dominant role in host immune responses to a myriad of biological triggers, including infections, cancers, and cardiovascular diseases. Current tools to probe these leukocytes inadequately profile these vital biomarkers; the need for sample preprocessing steps of cell lysis, labeling, washing, and pipetting inevitably triggers the cells, changes its basal state, and dilutes the individual cell secretion in bulk assays. Using a fully integrated system for multiplexed profiling of native immune single-cell enzyme secretion from 50 μL of undiluted blood, we eliminate sample handling. With a total analysis time of 60 min, the integrated platform performs six tasks of leukocyte extraction, cell washing, fluorescent enzyme substrate mixing, single-cell droplet making, droplet incubation, and real-time readout for leukocyte secretion profiling of neutrophil elastase, granzyme B, and metalloproteinase. We calibrated the device, optimized the protocols, and tested the leukocyte secretion of acute heart failure (AHF) patients at admission and predischarge. This paper highlights the presence of single-cell enzymatic immune phenotypes independent of CD marker labeling, which could potentially elucidate the innate immune response states. We found that patients recovering from AHF showed a corresponding reduction in immune-cell enzymatic secretion levels and donor-specific enzymatic signatures were observed, which suggests patient-to-patient heterogeneous immune response. This platform presents opportunities to elucidate the complexities of the immune response from a single drop of blood and bridge the current technological, biological, and medical gap in understanding immune response and biological triggers.

BackgroundLittle is known about the impact of the global coronavirus disease-2019 (COVID-19) pandemic on patients with cardiovascular disease (CVD), the biggest global killer and major risk factor for severe COVID-19 infections. We aim to explore the indirect consequences of COVID-19 on health-related quality of life (HRQoL) of patients with CVD.MethodsEighty-one adult outpatients with CVD were assessed using the EQ-5D, a generic health status instrument with five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), before and during the pandemic. Changes in the EQ-5D dimensional responses were compared categorically as well as using the dimension-specific sum-score (range 1 to 3, with a higher score indicating worse health). The responses and sum-score were compared using the exact test of symmetry and the paired t-test, respectively.ResultsThese patients [mean age (SD) 59.8 (10.5); 92.6% males; 56% New York Heart Association (NYHA) functional class I] had coronary artery disease (69%), heart failure (28%), or arrhythmias (15%). None experienced change in NYHA class between assessments.About 30% and 38% of patients reported problems with at least one of the EQ-5D dimensions pre-pandemic and during the pandemic, respectively. The highest increase in health problems was reported for anxiety/depression (12.5% pre-pandemic vs 23.5% during pandemic; p = 0.035) with mean domain-specific score from 1.12 (SD 0.33) to 1.25 (SD 0.46) (standardized effect size=0.373, p = 0.012). There was no meaningful change in other dimensions as well as overall HRQoL.ConclusionThe COVID-19 pandemic is associated with a significant worsening of the mental health of patients with CVD.

Aims Cardiorenal syndrome (CRS) is a common problem of great morbidity and mortality. Hydralazine-isosorbide dinitrate (H-ISDN) may be used in renal failure and may improve exercise capacity in heart failure (HF). Our proof-of-concept study aimed to evaluate early evidence of efficacy, safety, and feasibility of H-ISDN compared with standard of care in CRS. Methods and results This multi-centre, single-blind, randomized trial in Singapore enrolled CRS patients, defined as chronic HF with concomitant renal failure [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m 2 ]. The primary outcome was 6 min walk test (6MWT) distance measured at 6 months. Secondary outcomes included study feasibility; efficacy outcomes which included renal, cardiac, and endothelial functions, health-related quality of life using Short Form-36, clinical outcomes; and adverse events. Forty-four patients [71 ± 10 years; 75% male; median (inter-quartile range) N-terminal prohormone brain natriuretic peptide 1346 (481-2272) pg/mL] with CRS (left ventricular ejection fraction 42 ± 12% and eGFR 46 ± 15 ml/min/1.73 m 2) were randomized into two equal groups. Of these, 39 (89%) had hypertension, 27 (61%) had diabetes mellitus, and 17 (39%) had atrial fibrillation. Six (27%) discontinued H-ISDN owing to intolerance and poor compliance. There was a trend towards improved 6MWT distance with H-ISDN compared with standard of care at 6 months (mean difference 27 m; 95% CI, À12 to 66), with little differences in secondary efficacy outcomes. Giddiness and hypotension occurred more frequently with H-ISDN, but HF hospitalizations and mortality were less. Conclusions Our pilot study does not support the addition of H-ISDN on top of standard medical therapy to improve exercise capacity in patients with CRS.

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