Abstract Aims Quantitative methods have shown clinically significant heterogeneity in blood volume (BV) profiles across heart failure (HF) phenotypes. These profiles extend from hypovolaemia to normal BV and to variable degrees of BV hypervolaemia, frequently with similar clinical presentations. However, a comprehensive survey of BV profiles providing practical clinical guidance for the interpretation and management of quantitative plasma volume (PV) and red blood cell (RBC) mass findings has not been reported. The intent of this study is to advance this concept through a multicentre analysis. Methods and results A retrospective analysis of clinical and BV data was undertaken in stable NYHA class II–III HF patients (N = 546). BV was quantitated using established nuclear medicine indicator-dilution methodology. Differing combinations of PV and RBC mass were identified contributing to marked heterogeneity in overall BV profiles. A quantitatively normal BV was identified in 32% of the cohort but of these only ~1/3 demonstrated a true normal BV (i.e., normal PV + normal RBC mass). The remaining portion of normal BV profiles reflected balanced combinations of compensatory PV expansion with RBC mass deficit (anaemia) (14% of cohort) and PV contraction with RBC mass excess (erythrocythemia) (6% of cohort). Main contributors to BV hypervolaemia were PV excess with a normal RBC mass (21% of cohort; 23% female) and PV excess with erythrocythemia (24% of cohort; 26% female). Hypovolaemia was predominately defined by RBC mass deficit with a normal PV (6% of cohort; 57% female) or RBC mass deficit with PV contraction (5% of cohort; 48% female). Conclusions Findings support the clinical relevance of identifying and accurately interpreting the varying combinations of PV and RBC mass in patients with chronic HF. This in turn helps guide appropriate individualized patient management strategies. A practical volume-based guideline is provided in an effort to aid clinician interpretation.
A Comprehensive Evaluation of Risk Factors for Pneumocystis jirovecii Pneumonia in Adult Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis
Background. There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The 2019 American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) guidelines suggested to continue or reinstitute PJP prophylaxis in those receiving intensified immunosuppression for graft rejection, cytomegalovirus (CMV) infection, higher dose of corticosteroids, or prolonged neutropenia. Methods. A literature search was conducted evaluating all literature from existence through April 22, 2020, using MEDLINE and EMBASE. (The International Prospective Register of Systematic Reviews registration number: CRD42019134204). Results. A total of 30 studies with 413 276 SOT recipients were included. The following factors were associated with PJP development: acute rejection (pooled odds ratio [pOR], 2.35; 95% confidence interval [CI], 1.69-3.26); study heterogeneity index [I2] = 23.4%), CMV-related illnesses (pOR, 3.14; 95% CI, 2.30-4.29; I2 = 48%), absolute lymphocyte count <500 cells/mm3 (pOR, 6.29; 95% CI, 3.56-11.13; I2 = 0%), BK polyomavirus-related diseases (pOR, 2.59; 95% CI, 1.22-5.49; I2 = 0%), HLA mismatch ≥3 (pOR, 1.83; 95% CI, 1.06-3.17; I2 = 0%), rituximab use (pOR, 3.03; 95% CI, 1.82-5.04; I2 = 0%), and polyclonal antibodies use for rejection (pOR, 3.92; 95% CI, 1.87-8.19; I2 = 0%). On the other hand, sex, CMV mismatch, interleukin-2 inhibitors, corticosteroids for rejection, and plasmapheresis were not associated with developing PJP. Conclusions. PJP prophylaxis should be considered in SOT recipients with lymphopenia, BK polyomavirus-related infections, and rituximab exposure in addition to the previously mentioned risk factors in the American Society of Transplantation Infectious Diseases Community of Practice guidelines.
Angiotensin II antagonists and gastrointestinal bleeding in left ventricular assist devices: A systematic review and meta-analysis
Gastrointestinal bleeding (GIB) especially from arteriovenous malformations (AVM) remains one of the devastating complications following continuous-flow left ventricular device (CF-LVAD) implantation. Blockade of angiotensin II pathway using angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) was reported to mitigate the risk of GIB and AVM-related GIB by suppressing angiogenesis. We performed a systematic review and meta-analysis to evaluate the association between ACEI/ARB treatment and GIB in CF-LVAD population. Comprehensive literature search was performed through December 2019. We included studies reporting risk of GIB and/or AVM-related GIB events in LVAD patients who received ACEI/ARB with those who did not. Data from each study were combined using the random-effects to calculate odd ratios and 95% confidence intervals. Three retrospective cohort studies were included in this meta-analysis involving 619 LVADs patients (467 patients receiving ACEI/ARB). The use of ACEI/ARB was statistically associated with decreased incidence of overall GIB (pooled OR 0.35, 95% CI 0.22–0.56, I 2 = 0.0%, p < 0.001). There was a non-significant trend toward lower risk for AVM-related GIB in patients who received ACEI/ARB (pooled OR 0.46, 95% CI 0.19–1.07, I 2 = 51%, p = 0.07). Larger studies with specific definitions of ACEI/ARB use and GIB are warranted to accurately determine the potential non-hemodynamic benefits of ACEI/ARB in CF-LVAD patients.
Baseline significant tricuspid regurgitation is associated with higher mortality in transcatheter aortic valve replacement: systemic review and meta-analysis
Introduction Significant tricuspid regurgitation is a well recognized indicator of right ventricular dysfunction. Recent studies have shown that significant tricuspid regurgitation is potentially associated with increased mortality in patients with severe aortic stenosis who underwent transcatheter aortic valve replacement (TAVR). However, data remained sparse and inconclusive. Thus, we performed a systematic review and meta-analysis of the literature to assess the association between significant tricuspid regurgitation and mortality in post TAVR patients. Hypothesis Significant tricuspid regurgitation is predictive for higher mortality in patients undergoing TAVR. Methods We comprehensively searched the databases of MEDLINE and EMBASE from inception to October 2018. Included studies were published observational studies that reported multivariate analysis of the effects of significant tricuspid regurgitation on all-cause mortality among patients undergoing TAVR. Data from each study were combined utilizing the random-effects, generic inverse variance method of DerSimonian and Laird to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results Nine cohort studies from August 2011 to May 2018 consisting of 27 614 patients with severe aortic stenosis undergoing TAVR (6255 with and 21 359 without significant tricuspid regurgitation) were included in this meta-analysis. The presence of significant tricuspid regurgitation was associated with higher all-cause mortality (pooled OR = 2.26, 95% CI: 1.45–3.52, P < 0.001). We found that all-cause mortality remained statistically substantial in all subgroups (30-day all-cause mortality: OR = 2.05, 95% CI: 1.20–3.49, P = 0.009; midterm all-cause mortality: OR = 9.67, 95% CI: 2.44–38.31, P = 0.001; and long-term all-cause mortality: OR = 1.48, 95% CI: 1.19–1.85, P < 0.001). Funnel plots and Egger's regression asymmetry test were performed and showed no publication bias. Conclusion Significant tricuspid regurgitation increased risk of mortality by up to two-fold among patients with severe aortic stenosis undergoing TAVR. Our study suggests that significant tricuspid regurgitation should be considered a component of risk stratification tools.