Implementing a self-reported immunosuppression adherence questionnaire to screen for non-adherence in routine care of kidney transplant recipients.

INTRODUCTION: Self-reported measures of immunosuppression adherence have been largely examined in research settings. METHODS: In this single center study of 610 kidney transplant recipients, we examined if a voluntary, non-anonymous self-report measure could identify non-adherence in a routine clinic setting and how patients perceived such a measure. Non-adherence was measured using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and patient perception was elicited using a customized questionnaire. RESULTS: Non-responders to the survey (15%) were younger, more likely to be black, and less likely to have had a pre-emptive transplant. Among complete responders (n = 485), 38% reported non-adherence with non-adherent patients being younger (54 y vs. 60 y; p = .01), less likely to have been on dialysis pre-transplant (59% vs. 68%; p = .04), further out from transplant (37 vs. 22 months; p < .001) and had more rejections in the preceding year (8% vs. 3%; p = .02). Self-reported non-adherence was associated with higher calcineurin inhibitor intra-patient variability (27.4% vs. 24.5%; p = .02), but not with donor-specific antibody detection (27.8% vs. 21.2%, p = .15). Of patients providing feedback (n = 500), the majority of patients felt comfortable reporting adherence (92%), that the survey was relevant to their visit (71%), and that the survey did not interfere with their clinic visit (88%). CONCLUSION: In summary, a self-reported questionnaire during clinic visits identified immunosuppression non-adherence in a significant proportion of patients and was well received by patients. Integrating self-report measures into routine post-transplant care may enable early identification of non-adherence.

External validation of the SAVED score for venous thromboembolism risk stratification in patients with multiple myeloma receiving immunomodulatory drugs.

Selective patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiD) are at high risk for venous thromboembolism (VTE). The SAVED score is a VTE risk prediction model recently incorporated into the National Comprehensive Cancer Network (NCCN) guidelines. Using retrospective data from 501 MM patients with new IMiD initiation between 2010 and 2019, we performed the first independent external validation of this model. The cumulative incidence of VTE after IMiD initiation at 6 and 12 months was 32% and 42% in the high-risk group, versus 6% and 9% in the low-risk group respectively. The C-statistic of the SAVED score to predict VTE within 12 months of IMiD-based treatment start was 0.74 [95% confidence interval (CI): 0.69-0.78], which outperformed several other VTE risk models in MM patients. Our findings suggest that the SAVED score is an accurate risk assessment tool for VTE stratification in patients initiating IMiD-containing regimens.

Supplements for Lipid Lowering: What Does the Evidence Show?

PURPOSE: In this review, the regulation, proposed hypolipidemic mechanism, and efficacy of common dietary supplements (DSs) marketed for cardiovascular health are discussed. RECENT FINDINGS: Data demonstrate modest but inconsistent lipid-lowering effects with common DSs such as probiotics, soluble fibers, plant sterols, green tea, berberine, guggul, niacin, and garlic. Furthermore, data is limited regarding turmeric, hawthorn, and cinnamon. Red yeast rice has shown to be a beneficial DS, but its safety and efficacy are dependent upon its production quality and monacolin K content, respectively. Finally, soy proteins and omega-3 fatty acid-rich foods can have significant health benefits if used to displace other animal products as part of a healthier diet. Despite the rising use of DSs, data demonstrate unpredictable results. Patients should be educated on the difference between these DSs and evidence-based lipid-lowering medications proven to improve cardiovascular outcomes.

Impact of plasma volume status on mortality following left ventricular assist device implantation.

Worsening systemic congestion is often the central trigger of hospitalization in patients with heart failure. However, accurate assessment of congestion is challenging. The prognostic impact of systemic congestion following durable continuous-flow left ventricular assist device (LVAD) implantation remains unknown. Consecutive patients who received durable continuous-flow LVAD implantation between January 2014 and June 2017 and were followed for 1 year were included. The association of preoperative plasma volume status, which was calculated using patients' body weight and hematocrit and expressed as a deviation from ideal plasma volume, with 1-year mortality following LVAD implantation was investigated. In total, 186 patients (median 57 years and 138 males) were included. Baseline plasma volume status was -30.1% (-37.1%, -19.4%) on median. Eighty-eight patients (47%) had higher plasma volume status (>-29.8%), and their 1-year survival was significantly lower than those without (67% vs. 87%, P = .001). High plasma volume status was an independent predictor of 1-year death with an adjusted hazard ratio of 4.52 (95% confidence interval 1.52-13.5). Baseline systemic congestion, as defined by the high plasma volume status, was associated with higher mortality following durable continuous-flow LVAD implantation. The implication of improving preoperative plasma volume remains an area of needed investigation.

Effect of tobacco smoking on outcomes after left ventricular assist device implantation.

Despite the well-established correlation between the tobacco use and cardiovascular disease, little is known about postoperative outcomes following the left ventricular assist device (LVAD) implantation. We aimed to elucidate the effect of tobacco smoking on post-LVAD implant outcomes. Patients who received LVADs from 2013 to 2018 were retrospectively characterized as current, former, or never smokers at the time of implant. We examined 1-year survival, total hospital readmissions, and specific hospital readmissions for LVAD-related adverse events based on patient's smoking status. Of the enrolled patients (n = 292), 55% were former smokers, 33% were never smokers, and 11% were current smokers. The majority of patients were African-American (48%) with a median age of 58 years. Never smokers were younger and less likely to be Caucasian compared to former or current smokers (P < .05, for both). The category of former smokers had statistically comparable total readmission rates with never smokers (2.49 vs. 2.13 event/year), whereas current smokers had significantly higher rates compared to never smokers (2.81 events/year, P < .05), with odds ratio 2.12 (95% CI = 1.35-3.32) adjusted for age and Caucasian race for >5 times of total readmissions per year. The rates of driveline infection, stroke, and hemolysis were statistically comparable between the never smokers and former smokers, while current smokers had significantly higher rates compared to never smokers (P < .05 for all).

Perioperative improvement in serum albumin level in patients with left ventricular assist device.

BACKGROUND: The negative impact of baseline hypoalbuminemia on clinical outcome following left ventricular assist device (LVAD) implantation is well known. However, the implications of perioperative change in serum albumin levels on post-LVAD outcomes remain uninvestigated. METHODS: Among consecutive patients with baseline serum albumin <3.5 g/dl who received durable LVAD implantation between April 2014 and August 2017 and were followed for 1 year, the impact of perioperative change in serum albumin level from baseline to 3 months post-LVAD on the incidence of adverse events was investigated. RESULTS: Sixty-eight patients (median 60 years and 69% male) were included. Serum albumin change was an independent predictor of the occurrence of adverse events with an adjusted hazard ratio of 0.32 (95% confidence interval, 0.13-0.78) and a cutoff change of 0.7 g/dl. Those with albumin increase >0.7 g/dl had higher 1-year freedom from adverse events (45% vs. 14%, p = .008), dominantly due to lower incidence of death or sepsis compared with those without (p < .05 for both). CONCLUSION: Among those with baseline hypoalbuminemia, a considerable perioperative increase in serum albumin levels following LVAD implantation was associated with lower mortality and morbidity. The implication of aggressive nutrition intervention on LVAD patients is the next concern.

Sex difference in the impact of smoking on left ventricular assist device outcomes.

BACKGROUND: Active smoking is associated with worse clinical outcomes following left ventricular assist device (LVAD) implantation. However, the effect of sex differences in conjunction with smoking status remains uninvestigated. METHODS: Consecutive patients who underwent LVAD implantation between January 2013 and September 2018 were included. Clinical outcomes were retrospectively compared between the current smokers and never smokers among male cohorts and female cohorts separately. RESULTS: About 130 patients, with a median age of 56 years, were included. Among the male cohort (N = 85), the current smokers (N = 25/85) had a higher total readmission rate than the never smokers (N = 60/85) with an adjusted incidence rate ratio of 2.38 (95% confidence interval, 1.16-3.85, P = .014), dominantly due to higher rates of gastrointestinal bleeding, stroke, and hemolysis. Among the female cohorts (N = 45), never smokers (N = 36/45) had a statistically comparable total readmission rate (2.80 vs 2.50 events per year; P = .37) compared with current smokers (N = 9/45). CONCLUSION: Among male patients with LVAD, active smoking was associated with higher rates of adverse events. Female patients with LVAD had a high rate of adverse events irrespective of smoking status. Gender-specific therapeutic approaches might be required to prevent LVAD-related comorbidities.

Opioid Use and Morbidities during Left Ventricular Assist Device Support.

The use of opioids during left ventricular assist device (LVAD) support is increasing, but the implication remains unknown. We investigated the association between the use of opioid and morbidities during LVAD supports. We retrospectively reviewed the clinical data of patients who received LVAD between 2014 and 2017, which were stratified by the use of opioid at post-LVAD 3 months. Among 136 patients, 77 (57%) were in the opioid group. Hemoglobin and albumin were lower, and C-reactive protein was higher at baseline and 3 months later in the opioid group (P < 0.05 for all). The opioid group displayed worse hemodynamics, with higher pulmonary capillary wedge pressure and central venous pressure (P < 0.05 for both). Furthermore, the opioid group had higher incidences of gastrointestinal bleeding (31% versus 17%, P = 0.043) and sepsis (30% versus 13%, P = 0.036) during the 1 year observational period, whereas survivals were not stratified by the use of opioid (83% versus 90%, P = 0.27). Opioid use was associated with morbidities accompanied by poor hemodynamics during LVAD supports. The detailed causality of opioid use on morbidities remains a future concern.

Adenovirus-associated Acute Respiratory Distress Syndrome: Need for a Protocol-based Approach.

AIM: Viral causes of acute respiratory distress syndrome (ARDS) are mostly limited to influenza A; however, adenovirus has been emerging as a cause of fulminant ARDS with a high mortality rate and no consensus on its management. Here we present a series of five patients with confirmed adenovirus infection treated for ARDS at our quaternary referral institution. MATERIALS AND METHODS: All patients were above 18 years old, had confirmed adenovirus infection, and were treated for acute hypoxic respiratory failure requiring mechanical ventilation in our medical intensive care unit (MICU). Demographic and clinical data were collected and analyzed. RESULTS: Among these patients, the median age was 28 years, median BMI 28 kg/m2 median sequential organ failure assessment (SOFA) score 9, and median acute physiology and chronic health evaluation (APACHE) III score 74. All patients received lung-protective mechanical ventilation with high positive end-expiratory pressure and low plateau pressures. Three patients developed severe ARDS, two received prone position ventilation, and one was placed on extracorporeal membrane oxygenation. The median duration of mechanical ventilation, MICU length of stay, and hospital length of stay were 24, 19, and 27 days, respectively. One out of five patients died in our study. CONCLUSION: The mortality rate for adenovirus-associated pneumonia in the literature is estimated to be 40% in those requiring mechanical ventilation. The lower mortality at our institution could be attributed to the use of standardized protocols, which include low tidal volume ventilation, early use of neuromuscular blockade, targeting low plateau pressures, conservative fluid management, and comfort and familiarity with the use of adjunctive and rescue therapies. We recommend testing for adenovirus as part of a routine respiratory viral panel in ARDS patients, and if tested positive, transfer to tertiary or quaternary centers with the experience and rescue modalities needed to manage complicated ARDS patients. HOW TO CITE THIS ARTICLE: Vashisht R, Mirzai S, Koval C, Duggal A. Adenovirus-associated Acute Respiratory Distress Syndrome: Need for a Protocol-based Approach. Indian J Crit Care Med 2020;24(5):367-368.

Robotic totally endoscopic off-pump unroofing of left anterior descending coronary artery myocardial bridge: A report of two cases.

Myocardial bridge occurs when the myocardium courses external to an intramyocardial coronary artery, most commonly, the left anterior descending artery. The presentation can range from an asymptomatic, incidental finding to myocardial infarction, and sudden cardiac death. We report two cases of symptomatic MBs, which were treated with surgical unroofing, using a totally endoscopic robotic-assisted off-pump approach.

Skeletal muscle quantity and quality evaluation in heart failure: comparing thoracic versus abdominopelvic CT approaches.

Given the critical role of skeletal muscle in healthy aging, low muscle mass (myopenia) and quality (myosteatosis) can be used as predictors of poor functional and cardiometabolic outcomes. Myopenia is also a part of sarcopenia and malnutrition diagnostic criteria. However, there is limited evidence for using chest computed tomography (CT) to evaluate muscle health. We aimed to compare chest CT landmarks to the widely used L3 vertebra for single-slice skeletal muscle evaluation in patients with heart failure (HF). Patients admitted for acute decompensated HF between January 2017 and December 2018 were retrospectively analyzed. Body composition measurements were made on CT of the chest and abdomen/pelvis with or without contrast one month before discharge. Skeletal muscle index (SMI) and intermuscular adipose tissue percentage (IMAT%) were calculated at several thoracic levels (above the aortic arch, T8, and T12) and correlated to the widely used L3 level. A total of 200 patients were included, 89 (44.5%) female. The strongest correlation of thoracic SMI (for muscle quantity) and IMAT% (for muscle quality) with L3 was at the T12 level (r = 0.834, p < 0.001 and r = 0.757, p < 0.001, respectively). Cutoffs to identify low muscle mass for T12 SMI (derived from the lowest sex-stratified L3 SMI tertile) were 31.1 cm²/m² in men and 26.3 cm²/m² in women. SMI and IMAT% at T12 had excellent correlations with the widely used L3 level for muscle quantity and quality evaluation in patients with HF.

Sarcopenic Obesity and Cardiovascular Disease: An Overlooked but High-Risk Syndrome.

PURPOSE OF REVIEW: Sarcopenic obesity (SO), defined as the coexistence of excess fat mass and reduced skeletal muscle mass and strength, has emerged as an important cardiovascular risk factor, particularly in older adults. This review summarizes recent findings on the diagnosis, prevalence, health impacts, and treatment of SO. RECENT FINDINGS: Growing evidence suggests SO exacerbates cardiometabolic risk and adverse health outcomes beyond either condition alone; however, the heterogeneity in diagnostic criteria and the observational nature of most studies prohibit the evaluation of a causal relationship. This is concerning given that SO is increasing with the aging population, although that is also difficult to assess accurately given wide-ranging prevalence estimates. A recent consensus definition proposed by the European Society for Clinical Nutrition and Metabolism and the European Association for the Study of Obesity provides a framework of standardized criteria to diagnose SO. Adopting uniform diagnostic criteria for SO will enable more accurate characterization of prevalence and cardiometabolic risk moving forward. Although current management revolves around diet for weight loss coupled with resistance training to mitigate further muscle loss, emerging pharmacologic therapies have shown promising results. As the global population ages, diagnosing and managing SO will become imperative to alleviate the cardiovascular burden.

Quantifying lead-attributable cardiovascular disease burden in the United States.

Lead exposure has been linked to a myriad of cardiovascular diseases. Utilizing data from the 2019 Global Burden of Disease Study, we quantified age-standardized lead exposure-related mortality and disability-adjusted life years (DALYs) in the United States between 1990 and 2019. Our analysis revealed a substantial reduction in age-standardized cardiovascular disease (CVD) mortality attributable to lead exposure by 60 % (from 7.4 to 2.9 per 100,000), along with a concurrent decrease in age-standardized CVD DALYs by 66 % (from 143.2 to 48.7 per 100,000).

Combined Prognostic Impact of Low Muscle Mass and Hypoalbuminemia in Patients Hospitalized for Heart Failure: A Retrospective Cohort Study.

BACKGROUND: Sarcopenia and hypoalbuminemia have been identified as independent predictors of increased adverse outcomes, including mortality and readmissions, in hospitalized older adults with acute decompensated heart failure (ADHF). However, the impact of coexisting sarcopenia and hypoalbuminemia on morbidity and death in adults with ADHF has not yet been investigated. We aimed to investigate the combined effects of lower muscle mass (LMM) as a surrogate for sarcopenia and hypoalbuminemia on in-hospital and postdischarge outcomes of patients hospitalized for ADHF. METHODS AND RESULTS: A total of 385 patients admitted for ADHF between 2017 and 2020 at a single institution were retrospectively identified. Demographic and clinical data were collected, including serum albumin levels at admission and discharge. Skeletal muscle indices were derived from semi-automated segmentation software analysis on axial chest computed tomography at the twelfth vertebral level. Our analysis revealed that patients who had LMM with admission hypoalbuminemia experienced increased diagnoses of infection and delirium with longer hospital length of stay and more frequent discharge to a facility. Upon discharge, 27.9% of patients had higher muscle mass without discharge hypoalbuminemia (reference group), 9.7% had LMM without discharge hypoalbuminemia, 38.4% had higher muscle mass with discharge hypoalbuminemia, and 24.0% had LMM with discharge hypoalbuminemia; mortality rates were 37.6%, 51.4%, 48.9%, and 63.2%, respectively. 1- and 3-year mortality risks were highest in those with LMM and discharge hypoalbuminemia; this relationship remained significant over a median 23.6 (3.1-33.8) months follow-up time despite multivariable adjustments (hazard ratio, 2.03 [95% CI, 1.31-3.16]; P=0.002). CONCLUSIONS: Hospitalization with ADHF, LMM, and hypoalbuminemia portend heightened mortality risk.

Relationship Between Sarcopenia and Intensive Blood Pressure Control Efficacy and Safety: A Secondary Analysis of SPRINT.

BACKGROUND: Sarcopenia and hypertension are independently associated with worse cardiovascular disease (CVD) risk and survival. While individuals with sarcopenia may benefit from intensive blood pressure (BP) control, the increased vulnerability of this population raises concerns for potential harm. This study aimed to evaluate clinical and safety outcomes with intensive (target <120 mm Hg) versus standard (<140 mm Hg) BP targets in older hypertensive adults with sarcopenia compared with nonsarcopenic counterparts in the SPRINT (Systolic Blood Pressure Intervention Trial). METHODS: Sarcopenia was defined using surrogates of the lowest sex-stratified median of the sarcopenia index (serum creatinine/cystatin C×100) for muscle wasting and gait speed ≤0.8 m/s for muscle weakness. Outcomes included CVD events, all-cause mortality, and serious adverse events. RESULTS: Of 2571 SPRINT participants with sarcopenia index and gait speed data available (aged ≥75 years), 502 (19.5%) met the criteria for sarcopenia, which was associated with higher risks of CVD events (adjusted hazard ratio, 1.49 [95% CI, 1.15-1.94]; P=0.003) and all-cause mortality (adjusted hazard ratio, 1.46 [95% CI, 1.09-1.94]; P=0.010). In participants with sarcopenia, intensive (versus standard) BP control nearly halved the risk of CVD events (adjusted hazard ratio, 0.57 [95% CI, 0.36-0.88]; P=0.012) without increasing serious adverse events. Similar risk reduction was seen for all-cause mortality in participants with sarcopenia (adjusted hazard ratio, 0.66 [95% CI, 0.41-1.08]; P=0.102), but the effect was only significant in those without chronic kidney disease. CONCLUSIONS: Older hypertensive adults with sarcopenia randomized to intensive BP control experienced a lower risk of CVD without increased adverse events compared with standard BP control. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062.

Low Muscle Mass by Preprocedural Computed Tomography Is Associated With Worse Short-Term Outcomes in Transcatheter Aortic Valve Replacement Recipients.

Low muscle mass (LMM) is associated with worse outcomes in various clinical situations. Traditional frailty markers have been used for preoperative risk stratification in patients who underwent transcatheter aortic valve replacement (TAVR). However, preoperative imaging provides an opportunity to directly quantify skeletal muscle mass to identify patients at higher risk of procedural complications. We reviewed all TAVR recipients from January to December 2018 and included subjects with preprocedural chest computed tomography. Multi-slice automated measurements of skeletal muscle mass were made from the ninth to twelfth thoracic vertebrae and normalized by height squared to obtain skeletal muscle index (cm2/m2). LMM was defined as the lowest gender-stratified skeletal muscle index tertile. Strength testing was collected during pre-TAVR evaluation. Primary outcome was a composite of perioperative complications, 1-year rehospitalization, or 1-year mortality. In our cohort, 238 patients met inclusion criteria, and 80 (33.6%) were identified to have LMM. Patients with LMM were older with lower body mass index, decreased grip strength, lower hemoglobin A1c, and higher N-terminal pro-brain natriuretic peptide. They had greater rates of the composite outcome and 2-year all-cause mortality, which remained significant on multivariable adjustment (hazard ratio 1.71, 95% confidence interval 1.05 to 2.78, p = 0.030 and hazard ratio 2.31, 95% confidence interval 1.02 to 5.24, p = 0.045, respectively) compared with patients without LMM; there was no significant difference in 5-year all-cause mortality. In conclusion, LMM was associated with an increase in the primary composite outcome and 2-year all-cause mortality in TAVR recipients. Using automatic muscle processing software on pre-TAVR computed tomography scans may serve as an additional preoperative risk stratification tool.

Beyond monoclonal gammopathy of undetermined significance, clinical spectrum of immunoglobulin M gammopathy: a case series with focus on the diagnostic and management challenges.

Immunoglobulin M monoclonal gammopathy is detected in Waldenström macroglobulinemia (WM), a rare lymphoplasmacytic lymphoma with serum immunoglobulin M. We report three rare presentations with focus on diagnostic and management challenges of type I cryoglobulinemia, type II cryoglobulinemia, and Bing-Neel syndrome. In approximately 10% of WM cases, macroglobulins can precipitate to cryoglobulins. Type I and II cryoglobulinemia, representing 10-15% and 50-60% of WM cases, respectively, present with vasculitis and renal failure. Bing-Neel syndrome, representing 1% of WM patients, is a rare neurological complication with lymphoplasmacytic infiltration in the brain. WM diagnosis includes bone marrow biopsy, immunophenotypic analysis, and MYD88 L265P mutation. We initiated management of cryoglobulinemia with dexamethasone, rituximab, and cyclophosphamide; in Bing-Neel, bortezomib and dexamethasone, followed by a Bruton tyrosine kinase inhibitor.

Lymphoplasmacytic lymphoma (LPL) is an aberrant proliferation of plasma cells which may present as Waldenström macroglobulinemia, a disease characterized by high levels of immunoglobulin M that may result in deposition in bone marrow, spleen, and lymph nodes. The current understanding of clinical presentation is limited: patients with LPL may present with a wide range of symptoms related to paraproteinemia or tumor infiltration. This case series elucidates on specific and rare subsets of LPL, namely types I and II cryoglobulinemia and Bing­Neel syndrome. This report showcases the uncommon symptomatology of immunoglobulin M kappa deposition, such as kidney failure and neurological defects. The diagnostic and management challenges are of specific interest in this report, considering criteria, such as bone marrow biopsy, immunofixation, and cerebrospinal analysis. Literature on treatment protocols is equally limited and this report considers dexamethasone-rituximab-cyclophosphamide protocol and Bruton tyrosine kinase inhibitors compared to other common regimens. This report can be of great use to clinical oncologists by adding to the working knowledge on the rare manifestations of LPL and how to approach diagnostic and management challenges.

Significance of Adipose Tissue Quantity and Distribution on Obesity Paradox in Heart Failure.

Obesity is a predictor of the development of systolic and diastolic heart failure (HF), but once established, patients with HF and obesity have better outcomes than their leaner counterparts, a phenomenon termed the "obesity paradox." We sought to investigate the impact of adipose tissue quantity and distribution, measured by way of computed tomography, on outcomes in patients with HF. Patients admitted for acute decompensated HF between January 2017 to December 2018 were retrospectively analyzed. Body composition measurements were made on computed tomography of the abdomen/pelvis. Visceral, subcutaneous, and intermuscular adipose tissues were measured at the mid-third lumbar vertebra, along with skeletal muscle and waist circumference. Paracardial (pericardial and epicardial) adipose tissue was measured at the mid-eight thoracic vertebra. Visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI), along with skeletal muscle index, were indexed for patient height. A total of 200 patients were included, 44.5% female. Body mass index and waist circumference did not significantly predict outcomes. Patients with high SATI (highest sex-stratified tertile) had significantly better survival (hazard ratio 0.58, 95% confidence interval 0.39 to 0.87, p = 0.009), whereas high VATI was nonsignificant. Patients were further divided into 4 groups based on both VATI and SATI. One- and 4-year mortality risks were lowest in those with low VATI high SATI compared with the other groups; this persisted after multivariable adjustment for covariates, including albumin and skeletal muscle index. In conclusion, the "obesity paradox" appears to be largely driven by subcutaneous adipose tissue, independent of nutrition or skeletal muscle.