RNase2 is a possible trigger of acute-on-chronic inflammation leading to mRNA vaccine-associated cardiac complication.

BACKGROUND: Post-mRNA vaccination-associated cardiac complication is a rare but life-threatening adverse event. Its risk has been well balanced by the benefit of vaccination-induced protection against severe COVID-19. As the rate of severe COVID-19 has consequently declined, future booster vaccination to sustain immunity, especially against infection with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, may encounter benefit-risk ratios that are less favorable than at the start of the COVID-19 vaccination campaign. Understanding the pathogenesis of rare but severe vaccine-associated adverse events to minimize its risk is thus urgent. METHODS: Here, we report a serendipitous finding of a case of cardiac complication following a third shot of COVID-19 mRNA vaccine. As this case was enrolled in a cohort study, pre-vaccination and pre-symptomatic blood samples were available for genomic and multiplex cytokine analyses. FINDINGS: These analyses revealed the presence of subclinical chronic inflammation, with an elevated expression of RNASE2 at pre-booster baseline as a possible trigger of an acute-on-chronic inflammation that resulted in the cardiac complication. RNASE2 encodes for the ribonuclease RNase2, which cleaves RNA at the 3' side of uridine, which may thus remove the only Toll-like receptor (TLR)-avoidance safety feature of current mRNA vaccines. CONCLUSIONS: These pre-booster and pre-symptomatic gene and cytokine expression data provide unique insights into the possible pathogenesis of vaccine-associated cardiac complication and suggest the incorporation of additional nucleoside modification for an added safety margin. FUNDING: This work was funded by the NMRC Open Fund-Large Collaborative Grant on Integrated Innovations on Infectious Diseases (OFLCG19May-0034).

Predicting premature termination of exercise during Bruce protocol stress echocardiography.

AIMS: Clinical guidelines recommend that the exercise protocol of a stress echocardiogram is selected to induce volitional exhaustion after a target duration of at least 8 minutes. While the Bruce protocol is very commonly used for clinical stress tests, it is known to be "steep", and many patients therefore fail to reach 8 minutes. We studied predictors of failure and developed a method for identifying patients not suitable for Bruce protocol which was accurate and yet simple enough to be used as a point-of-care decision support tool. METHODS AND RESULTS: We studied data out-patients undergoing Bruce protocol stress echocardiograms (n = 11 086) and analyzed predictors of inappropriate early termination (defined as test duration < 8 min as per current practice guidelines) using logistic regression. A prediction model was constructed as follows: .5 points were given for each of hypertension, diabetes, smoking, and E/e' > 7.9 in the resting echocardiogram; .1 point was added for each 1-unit increment in body mass index; 1 point was added for patient age by decade; 2.0 points were subtracted for male sex (p for all < 0.001). In tests on held-out validation data, the model was well calibrated (in plots of predicted vs actual risk) and discriminated failure versus non-failure well (C-statistic .86 for a score of 6.0 points; p < 0.001). CONCLUSION: These data may help to standardize protocol selection in stress echocardiography, by identifying patients pre-hoc where Bruce protocol will be inappropriately steep.

Prevalence, Presentation, and Outcome of Heart Failure with Preserved Ejection Fraction among Patients Presenting with Undifferentiated Dyspnoea to the Emergency Room: A 10-year Analysis from a Tertiary Centre.

INTRODUCTION: We assessed the local prevalence, characteristics and 10-year outcomes in a heart failure (HF) cohort from the emergency room (ER). MATERIALS AND METHODS: Patients presenting with acute dyspnoea to ER were prospectively enrolled from December 2003 to December 2004. HF was diagnosed by physicians' adjudication based on clinical assessment and echocardiogram within 12 hours, blinded to N-terminal-pro brain natriuretic peptide (NT-proBNP) results. They were stratified into heart failure with preserved (HFPEF) and reduced ejection fraction (HFREF) by left ventricular ejection fraction (LVEF). RESULTS: At different cutoffs of LVEF of ≥50%, ≥45%, ≥40%, and >50% plus excluding LVEF 40% to 50%, HFPEF prevalence ranged from 38% to 51%. Using LVEF ≥50% as the final cutoff point, at baseline, HFPEF (n = 35), compared to HFREF (n = 55), had lower admission NT- proBNP (1502 vs 5953 pg/mL, P <0.001), heart rate (86 ± 22 vs 98 ± 22 bpm, P = 0.014), and diastolic blood pressure (DBP) (75 ± 14 vs 84 ± 20 mmHg, P = 0.024). On echocardiogram, compared to HFREF, HFPEF had more LV concentric remodelling (20% vs 2%, P = 0.003), less eccentric hypertrophy (11% vs 53%, P <0.001) and less mitral regurgitation from functional mitral regurgitation (60% vs 95%, P = 0.027). At 10 years, compared to HFREF, HFPEF had similar primary endpoints of a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and rehospitalisation for congestive heart failure (CHF) (HR 0.886; 95% CI, 0.561 to 1.399; P = 0.605), all-cause mortality (HR 0.663; 95% CI, 0.400 to 1.100; P = 0.112), but lower cardiovascular mortality (HR 0.307; 95% CI, 0.111 to 0.850; P = 0.023). CONCLUSION: In the long term, HFPEF had higher non-cardiovascular mortality, but lower cardiovascular mortality compared to HFREF.

Heart failure as the first manifestation of renal cell carcinoma

We report the rare case of a patient with advanced renal cell carcinoma (RCC) who initially presented to the hospital with symptoms of cardiac failure. Preoperative cardiac studies did not reveal any underlying ischemia. After resection of a large 14-cm left renal tumor, cardiac function was noted to improve dramatically. We discuss this case of concomitant RCC and nonischemic cardiomyopathy.

How should I treat a percutaneous transcatheter mitral paravalvular leak closure?

BACKGROUND: A 49-year-old female presented with worsening exertional dyspnea (NYHA class III) and orthopnea for several months. Previous medical history was significant for rheumatic mitral regurgitation and three previous mitral valve replacements (MVRs). INVESTIGATION: Transesophageal echocardiography (TEE) revealed severe mitral paravalvular leak (PVL with two jets visualised. Cardiac computed tomography angiography (CTA) revealed a larger PVL and a smaller defect. DIAGNOSIS: Severe mitral paravalvular leak. TREATMENT: Transcatheter mitral paravalvular closure.