Associations of adipose tissue depots with cardiac resynchronization therapy response and clinical outcomes: A CRT-HF Clinic substudy.

BACKGROUND: The region of adipose deposition is an important determinant in the outcomes of patients with heart failure (HF). However, the impact of regional adiposity on HF patients undergoing cardiac resynchronization therapy (CRT) remains unclear. METHODS: A retrospective cohort analysis was conducted on 95 patients from a single-center study, assessing post-CRT outcomes. Multi-slice body composition measurements of chest computed tomography before CRT placement were used for adipose quantification. Patients were stratified based on subcutaneous adiposity, intramuscular adiposity, and hepatic steatosis. RESULTS/CONCLUSION: Subcutaneous adiposity correlated with higher CRT response rates (44.4 % in subcutaneous adiposity vs 16.7 % in subcutaneous adipopenia, p = 0.009), while intramuscular adiposity was associated with increased pre-frailty (adjusted OR 14.17, 95 % CI 2.24-89.57, p = 0.005). The higher response to CRT in patients with subcutaneous adiposity may be secondary to preferred subcutaneous over ectopic adipose fat deposition, which is potentially protective against cardiomyocyte dysfunction. Thus, intramuscular adiposity could potentially serve as a prognostic tool for frailty in HF patients.

Sarcopenia and frailty in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Skeletal muscle mass (SMM) plays a crucial role in risk assessment in transcatheter aortic valve replacement (TAVR) candidates, yet it remains underutilized. Traditional methods focus on weakness or performance but omit SMM. This study compared traditional and novel markers of sarcopenia and frailty in terms of their ability to predict adverse outcomes post-TAVR. METHODS: Three risk models were evaluated for the composite outcome of perioperative complications, 1-year rehospitalization, or 1-year mortality: (1) sarcopenia by combining low muscle mass (LMM) and weakness/performance assessed by hand grip strength or gait speed; (2) frailty by an Adapted Green score; and (3) frailty by the Green-SMI score incorporating LMM by multilevel opportunistic pre-TAVR thoracic CT segmentation. RESULTS: In this study we included 184 eligible patients from January to December of 2018, (96.7%) of which were balloon expandable valves. The three risk models identified 22.8% patients as sarcopenic, 63.6% as frail by the Adapted Green score, and 53.8% as frail by the Green-SMI score. There were higher rates of the composite outcome in patients with sarcopenia (54.8%) and frailty (41.9% with the Adapted Green and 50.5% with the Green-SMI score) compared to their nonsarcopenic (30.3%) and nonfrail counterparts (25.4% with the Adapted Green and 18.8% with the Green-SMI score). Sarcopenia and frailty by Green-SMI, but not by the Adapted Green, were associated with higher risks of the composite outcome on multivariable adjustment (HR 2.2 [95% CI: 1.25-4.02], P = .007 and HR 3.4 [95% CI: 1.75-6.65], P < .001, respectively). CONCLUSIONS: The integration of preoperative CT-based SMM to a frailty score significantly improves the prediction of adverse outcomes in patients undergoing TAVR.

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.

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) systolic 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.

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).

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.

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.

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.

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.

Clinical outcomes following tricuspid transcatheter edge-to-edge repair with PASCAL: A meta-analysis.

BACKGROUND: Patients with severe tricuspid regurgitation (TR) exhibit high morbidity and mortality. Tricuspid transcatheter edge-to-edge repair (T-TEER) is a rapidly evolving strategy to address the unmet clinical need of severe TR therapies. OBJECTIVE: Organize the current body of evidence on outcomes following use of the PASCAL (Edwards Lifesciences) system for T-TEER. METHODS: For this meta-analysis, we searched the MEDLINE/PubMed, Embase, and Cochrane databases for keywords ["tricuspid"] and ["transcatheter" or "edge-to-edge"] and ["PASCAL" or "leaflet repair" or "valve repair"] from the database inception until January 11, 2023. Primary outcomes of interest were procedural success, mortality, New York Heart Association (NYHA) functional class, 6-min walking distance (6MWD), and TR severity. RESULTS: A total of 549 patients undergoing PASCAL or PASCAL Ace T-TEER were included. The mean age ranged from 71.0 to 80.3 years, with 25.0 to 63.6% females. The follow-up duration ranged from 30 days to 1 year. The success rate was 83.5% (409/490). There was improvement in symptoms based on NYHA classification (at 1- to 6-months; NYHA ≥3 RR 0.27 [95% CI 0.19-0.39]; p < 0.001) and 6MWD (at 1-month; 50.96 [95% CI 32.34-69.59]; p < 0.001) post-procedure. On imaging, there was improvement in TR severity post-procedure (at 1- to 12-months; ≥ severe TR 0.21 [95% CI 0.14-0.31]; p < 0.001), which remained significant with each study removed. CONCLUSION: PASCAL for T-TEER is associated with high procedural success rates along with improvements in NYHA functional class, TR severity, 6MWD, and patient-reported outcomes.

Sarcopenia evaluation on cardiac magnetic resonance imaging in older adults for outcomes prediction following surgical aortic valve replacement.

BACKGROUND: Sarcopenia refers to a reduction in skeletal muscle mass and strength. Despite the known association between single-slice muscle measurements on lumbar computed tomography and poor outcomes in various clinical settings, studies using thoracic muscle measurements on cardiac magnetic resonance imaging (CMR) have been limited. METHODS: Patients undergoing surgical aortic valve replacement (SAVR) between 2010 and 2020 were included if they were ≥ 50 years of age with preoperative CMR. Manual unilateral pectoralis major and minor skeletal muscle area measurements were made at the carina and normalized for body size by height to obtain skeletal muscle index (SMI). Sarcopenia was defined as the lowest sex-stratified SMI tertile and higher-risk as the highest fiftieth percentile Society of Thoracic Surgeons' (STS) mortality score. RESULTS: A total of 133 patients were included, 35 (26.3%) females. The average age was 64 ± 9 years, with most Caucasian (93.2%). Compared to non-sarcopenic patients, sarcopenic patients were older with lower body mass index. During a median follow-up of 27.3 (7.6-60.4) months, 10 (22.2%) deaths occurred in the sarcopenic group and 8 (9.1%) in the non-sarcopenic group (p = 0.039 by log-rank test). On subgroup analysis (66 patients), higher-risk sarcopenic patients had 10 (37.0%) deaths compared to 8 (20.5%) in higher-risk non-sarcopenic patients (p = 0.011 by log-rank test). CONCLUSIONS: Simple unilateral pectoralis muscle measurements on preoperative CMR can be used as an adjunct to traditional risk scores for predicting mortality post-SAVR.

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.

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.

Ross procedure after prosthetic valve thrombosis in a patient with antiphospholipid syndrome and recurrent bleeding.

The Ross procedure allows replacement of a diseased aortic valve with pulmonary root autograft, possibly avoiding the highly thrombotic mechanical valves and immunologic deterioration of tissue valves in antiphospholipid syndrome (APS). Here, we present the use of the Ross procedure in a 42-year-old woman with mild intellectual disability, APS, and a complex anticoagulation history after she presented with thrombosis of her mechanical On-X aortic valve previously implanted for non-bacterial thrombotic endocarditis.

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.