Blood Volume Analysis and Cardio-renal syndrome: from bench to bedside.

BACKGROUND: This review delves into the intricate landscape of cardiorenal syndrome (CRS) and highlights the pivotal role of Blood Volume Analysis (BVA) in improving patient care and outcomes. SUMMARY: BVA offers a direct and highly accurate quantification of intravascular volume, red blood cell volume, and plasma volume, complete with patient-specific norms. This diagnostic tool enhances the precision of diuretic and red cell therapies, significantly elevating the effectiveness of conventional care. KEY MESSAGES: · Comprehensive Understanding: Our objectives encompass a comprehensive understanding of how BVA informs the evaluation and treatment of CRS, including its subtypes, pathophysiology, and clinical significance. · BVA Principles and Advantages: We delve into BVA principles, techniques, and measurements, elucidating its diagnostic potential and advantages compared to commonly used surrogate measures. · Clinical Relevance: We dissect the clinical relevance of BVA in various CRS scenarios, emphasizing its unique contributions to each subtype. · Improving patient outcomes: By assessing the tangible impact of BVA on patient outcomes through meticulous analysis of relevant clinical studies, we unveil its potential to enhance health outcomes and optimize resource utilization. · Multidisciplinary Collaboration: Acknowledging the challenges and limitations associated with BVA's clinical implementation, we underscore the importance of multidisciplinary collaboration among cardiologists, nephrologists, and other clinicians. · Future Directions: Finally, we identify research gaps and propose future directions for BVA and CRS, contributing to ongoing advancements in this field and patients affected by this complicated clinical syndrome.

Blood Volume Analysis of Total Artificial Heart Recipients: A Case Series.

Blood volume analysis provides a quantitative volume assessment in patients with equivocal or discordant clinical findings. Reports on its use in mechanical circulatory support are limited and it has never been described in patients with a total artificial heart. Our series demonstrates that patients supported with total artificial heart as a bridge to transplant have significant reductions in red blood cell volume and heterogeneous adaptations in their total blood volume and plasma volume. Pathologic derangements in our patient's total blood volume were targeted to restore euvolemia.

Prognostic implications of volume status assessed by blood volume analysis in ambulatory heart failure.

The prognostic implications of intravascular volume status assessed by blood volume analysis (BVA) in ambulatory heart failure (HF) remain uncertain. The incremental benefits of assessing volume status, beyond the well-established filling pressures, in predicting HF outcomes are unknown.

Serial blood volume measurements in patients with compensated chronic heart failure: How do volume profiles change over time?

Among patients with chronic heart failure (HF) intravascular volume profiles vary significantly despite similar clinical compensation. However, little is known regarding changes in blood volume (BV) profiles over time. The objective of this analysis was to identify the extent and character of changes in volume profiles over time. A prospective analysis was undertaken in patients who were hospitalized and treated for fluid overload. Quantitative BV analyses were obtained in a compensated state at hospital discharge (baseline) and follow-up at 1, 3, and 6 mo. Data were available on 10 patients who remained stable without rehospitalization or medication change over a 6-mo period. Baseline BV profiles were highly variable at hospital discharge with an average deviation of +28% above normal in 6 patients and normal BV in 4 patients. Over the follow-up period, the median change in BV was -201 mL [-3% (-6, +3%)] from baseline with profiles remaining in the same volume category in 9 out of 10 patients. Crossover from normal BV to mild contraction (-13% of normal) occurred in one patient. Red blood cell mass demonstrated the largest change over 6 mo [median -275 (-410, +175) mL] with a deviation from normal of -14 (-20, +8) % (reflecting mild anemia). These findings suggest that BV profiles in clinically compensated patients with HF do not change substantially over a 6-mo period regardless of baseline expanded or normal BV. This lack of change in volume profiles particularly from an expanded BV has implications for long-term volume management, clinical outcomes, and also our understanding of volume homeostasis in HF.NEW & NOTEWORTHY The novel findings of this study demonstrate that blood volume profiles while highly variable in clinically compensated patients with HF on stable medical therapy do not change substantially over a 6-mo period regardless of baseline expanded or normal blood volumes. This lack of change in volume profiles particularly from an expanded blood volume has implications for long-term volume management and also for how we understand the pathophysiology of volume homeostasis in chronic HF.

Pressure-Volume Profiles in Heart Failure Across Sexes and Phenotypes.

Studies have shown poor correlation between intra-cardiac pressures and blood volume (BV) measurements including HF. The impact of sex and left ventricular ejection fraction (LVEF) on this relationship has not been studied. We obtained pressure (pulmonary artery diastolic pressure (PADP)) and volume (total blood volume (TBV) and estimated stress blood volume (eSBV)) measurements from HF patients at the time of CardioMEMS implantation. A total of 20 patients were included. There was no significant difference between PADP, TBV, and eSBV between sexes. There was only a moderate correlation between PADP and eSBV in men but not in women or with TBV in both sexes. HFrEF had higher PADP and eSBV than HFpEF. There was a consistent lack of correlation between PADP and both TBV and eSBV. Further studies evaluating mid- to long-term implications of pressure-volume profiles as well as changes following decongestion therapy are warranted to better understand the pressure-volume interplay and determine appropriate decongestion strategy for each pressure-volume phenotype.

Can heat therapy help patients with heart failure?

To review and analyze the clinical outcomes of thermal therapy (≤1.4°C increase in core body temperature) in patients with heart failure (HF). A systematic review and meta-analysis regarding the effects of thermal therapy on HF was done by searching PubMed, Ovid Medline, Ovid Embase, Scopus, and internal databases up to date (2019). Improvement in the New York Heart Association (NYHA) class: Ten studies with 310 patients showed significant improvement in NYHA class. Only 7 among 40 patients remained in Class IV and 99 patients in Class III from 155 patients. Increased patients in lower classes indicate that more patients showed improvement. Sixteen studies on 506 patients showed an overall improvement of 4.4% of left ventricular ejection fraction (LVEF). Four studies reported improved endothelial dysfunction by 1.7% increase in flow-mediated dilation (FMD) on 130 patients. Reduction in blood pressure: Thermal therapy reduced both systolic blood pressure (SBP) and diastolic blood pressure by 3.1% and 5.31%, respectively, in 431 patients of 15 studies. Decrease in cardiothoracic ratio (CTR): Eight studies reported an average of 5.55% reduction of CTR in a total of 347 patients. Improvement in oxidative stress markers: Plasma brain natriuretic peptide (BNP) levels significantly decreased (mean difference of 14.8 pg/dL) in 303 patients of 9 studies. Improvement of quality of life: Among 65 patients, thermal therapy reduced cardiac death and rehospitalization by 31.3%. A slight increase in core body temperature is a promising, noninvasive, effective, and complementary therapy for patients with HF. Further clinical studies are recommended.

Home Hospitalization for Acute Decompensated Heart Failure: Opportunities and Strategies for Improved Health Outcomes.

IMPORTANCE: Heart failure (HF) is the leading cause of hospitalization among patients over the age of 65 in the United States and developed countries, posing a significant economic burden to the health care systems. More than half of the patients with HF will be readmitted to the hospital within 6 months from discharge, leading not only to increased health care related expenses but also functional decline, iatrogenic injuries and in-hospital infections. With the increasing prevalence of HF, there is a substantial need for innovative delivery care models that can provide hospital level of care at a patient's home. OBSERVATIONS: Home hospitalization was originally used to safely manage chronically ill patients with general medical (stroke, chronic obstructive pulmonary disease, deep vein thrombosis, community acquired pneumonia) and surgical conditions and was associated with improved patient satisfaction and improvement in activity of daily living status. This had no clear effect on readmission or cost. When hospital at home care model was applied to HF patients it demonstrated increased time to readmission, reduced index costs and improved health related quality of life, with no significant differences in adverse events. Eligible patients should be selected based on multiple factors taking into consideration applicable limitations and comorbidities. CONCLUSIONS AND RELEVANCE: Providing in-hospital level care to the patient's house presents a reliable alternative, yielding multiple benefits both for the patient, as well as the health care system. Formulating a well-defined model is necessary before wide implementation.

Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey).

BACKGROUND: Transthyretin amyloidosis (ATTR) is a heterogeneous disorder with multiorgan involvement and a genetic or nongenetic basis. OBJECTIVES: The goal of this study was to describe ATTR in the United States by using data from the THAOS (Transthyretin Amyloidosis Outcomes Survey) registry. METHODS: Demographic, clinical, and genetic features of patients enrolled in the THAOS registry in the United States (n = 390) were compared with data from patients from other regions of the world (ROW) (n = 2,140). The focus was on the phenotypic expression and survival in the majority of U.S. subjects with valine-to-isoleucine substitution at position 122 (Val122Ile) (n = 91) and wild-type ATTR (n = 189). RESULTS: U.S. subjects are older (70 vs. 46 years), more often male (85.4% vs. 50.6%), and more often of African descent (25.4% vs. 0.5%) than the ROW. A significantly higher percentage of U.S. patients with ATTR amyloid seen at cardiology sites had wild-type disease than the ROW (50.5% vs. 26.2%). In the United States, 34 different mutations (n = 201) have been reported, with the most common being Val122Ile (n = 91; 45.3%) and Thr60Ala (n = 41; 20.4%). Overall, 91 (85%) of 107 patients with Val122Ile were from the United States, where Val122Ile subjects were younger and more often female and black than patients with wild-type disease, and had similar cardiac phenotype but a greater burden of neurologic symptoms (pain, numbness, tingling, and walking disability) and worse quality of life. Advancing age and lower mean arterial pressure, but not the presence of a transthyretin mutation, were independently associated with higher mortality from a multivariate analysis of survival. CONCLUSIONS: In the THAOS registry, ATTR in the United States is overwhelmingly a disorder of older adult male subjects with a cardiac-predominant phenotype. Val122Ile is the most common transthyretin mutation, and neurologic phenotypic expression differs between wild-type disease and Val122Ile, but survival from enrollment in THAOS does not. (Transthyretin-Associated Amyloidoses Outcome Survey [THAOS]; NCT00628745).

Impact of Enhanced External Counterpulsation on Heart Failure Rehospitalization in Patients With Ischemic Cardiomyopathy.

Heart failure (HF) affects millions of Americans and causes financial burdens because of the need for rehospitalization. For this reason, health care systems and patients alike are seeking methods to decrease readmissions. We assessed the potential for reducing readmissions of patients with postacute care HF through an educational program combined with enhanced external counterpulsation (EECP). We examined 99 patients with HF who were referred to EECP centers and received heart failure education and EECP treatment within 90 days of hospital discharge from March 2013 to January 2015. We compared observed and predicted 90-day readmission rates and examined results of 6-minute walk tests, Duke Activity Status Index, New York Heart Association classification, and Canadian Cardiovascular Society classification before and after EECP. Patients were treated with EECP at a median augmentation pressure of 280 mm Hg (quartile 1 = 240, quartile 3 = 280), achieved as early as the first treatment. Augmentation ratios varied from 0.4 to 1.9, with a median of 1.0 (quartile 1 = 0.8, quartile 3 = 1.2). Only 6 patients (6.1%) had unplanned readmissions compared to the predicted 34%, p <0.0001. The average increase in distance walked was 52 m (18.4%), and the median increase in Duke Activity Status Index was 9.95 points (100%), p values <0.0001. New York Heart Association and Canadian Cardiovascular Society classes improved in 61% and 60% of the patients, respectively. In conclusion, patients with HF who received education and EECP within 90 days of discharge had significantly lower readmission rates than predicted, and improved functional status, walk distance, and symptoms.

A Review of the DASH Diet as an Optimal Dietary Plan for Symptomatic Heart Failure.

Despite tremendous focus, effort, drug and device development and resources dedicated to the care of patients at risk for and with heart failure (HF), the epidemic continues. The HF patient presents with a widely deranged physiology and typically at the same time is malnourished adding to the disease complexity and therapeutic challenges. Most nutritional approaches for patients with HF focus on dietary restrictions (of salt and water) and lack uniformity or clarity or focus on meeting nutritional needs, barriers and deficits of the patient with HF. Finally, it seems reasonable to anticipate that any dietary program recommendation should contribute in a positive way toward HF management goals and at its foundation positively contribute to the deranged physiology. In many ways the "Dietary Approaches to Stop Hypertension" (DASH) dietary program fulfills these needs and early evidence supports the notion that the DASH diet may be optimal for patients with HF. This brief review examines some of this evidence and provides recommendations for the HF community.

Impact of the DASH diet on endothelial function, exercise capacity, and quality of life in patients with heart failure.

Endothelial dysfunction has been recognized as a pathophysiologic mechanism in the progression of heart failure (HF). However, little attention has been given to the ability of dietary approaches to improve endothelial function. This study examined the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on endothelial function, exercise capacity, and quality of life in patients with chronic symptomatic (stage C) HF. Forty-eight patients were randomized to follow the DASH diet (n = 24) or the general HF dietary recommendations (n = 24). Endothelial function was assessed by measuring large and small arterial elasticity (LAE and SAE) at rest. Exercise capacity (measured with the 6-minute walk test) and quality of life (measured with the Minnesota Living with Heart Failure Questionnaire) at baseline and 3 months were also evaluated. Patients were older adults with an average HF duration of 5 years. LAE at 1 month improved significantly in the DASH diet group (P < 0.01). Overall LAE and SAE scores at 3 months also improved; however, the net changes were not statistically significant. The DASH group had better exercise capacity (292 m vs 197 m; P = 0.018) and quality of life scores (21 vs 39; P = 0.006) over time, while sodium intake levels at 1, 2, and 3 months were comparable between the groups. Adhering to the DASH diet improved arterial compliance initially and improved exercise capacity and quality of life scores at 3 months. The DASH diet may be an important adjunctive therapy for patients with symptomatic HF.

Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation.

AIMS: There is little evidence of beta-blocker treatment benefit in patients with heart failure and reduced left ventricular ejection fraction (HFREF) and atrial fibrillation (AF). We investigated the effects of bucindolol in HFREF patients with AF enrolled in the Beta-blocker Evaluation of Survival Trial (BEST). METHODS AND RESULTS: A post-hoc analysis of patients in BEST with and without AF was performed to estimate the effect of bucindolol on mortality and hospitalization. Patients were also evaluated for treatment effects on heart rate and the influence of beta1-adrenergic receptor position 389 (ß(1)389) arginine (Arg) vs. glycine (Gly) genotypes. In the 303/2708 patients in AF, patients receiving bucindolol were more likely to achieve a resting heart rate ≤ 80 b.p.m. at 3 months (P < 0.005) in the absence of treatment-limiting bradycardia. In AF patients and sinus rhythm (SR) patients who achieved a resting heart rate ≤ 80 b.p.m., there were beneficial treatment effects on cardiovascular mortality/cardiovascular hospitalization [hazard ratio (HR) 0.61, P = 0.025, and 0.79, P = 0.002]. Without achieving a resting heart rate ≤ 80 b.p.m., there were no treatment effects on events in either group. ß(1)389-Arg/Arg AF patients had nominally significant reductions in all-cause mortality/HF hospitalization and cardiovascular mortality/hospitalization with bucindolol (HR 0.23, P = 0.037 and 0.28, P = 0.039), whereas Gly carriers did not. There was no evidence of diminished heart rate response in ß(1)389-Arg homozygotes. CONCLUSION: In HFREF patients with AF, bucindolol was associated with reductions in composite HF endpoints in those who achieved a resting heart rate ≤ 80 b.p.m. and nominally in those with the ß(1)389-Arg homozygous genotype.

Combinatorial pharmacogenetic interactions of bucindolol and ß1, α2C adrenergic receptor polymorphisms.

BACKGROUND: Pharmacogenetics involves complex interactions of gene products affecting pharmacodynamics and pharmacokinetics, but there is little information on the interaction of multiple genetic modifiers of drug response. Bucindolol is a ß-blocker/sympatholytic agent whose efficacy is modulated by polymorphisms in the primary target (ß(1) adrenergic receptor [AR] Arg389 Gly on cardiac myocytes) and a secondary target modifier (α(2C) AR Ins [wild-type (Wt)] 322-325 deletion [Del] on cardiac adrenergic neurons). The major allele homozygotes and minor allele carriers of each polymorphism are respectively associated with efficacy enhancement and loss, creating the possibility for genotype combination interactions that can be measured by clinical trial methodology. METHODOLOGY: In a 1,040 patient substudy of a bucindolol vs. placebo heart failure clinical trial, we tested the hypothesis that combinations of ß(1)389 and α(2C)322-325 polymorphisms are additive for both efficacy enhancement and loss. Additionally, norepinephrine (NE) affinity for ß(1)389 AR variants was measured in human explanted left ventricles. PRINCIPAL FINDINGS: The combination of ß(1)389 Arg+α(2C)322-325 Wt major allele homozygotes (47% of the trial population) was non-additive for efficacy enhancement across six clinical endpoints, with an average efficacy increase of 1.70-fold vs. 2.32-fold in ß(1)389 Arg homozygotes+α(2C)322-325 Del minor allele carriers. In contrast, the minor allele carrier combination (13% subset) exhibited additive efficacy loss. These disparate effects are likely due to the higher proportion (42% vs. 8.7%, P = 0.009) of high-affinity NE binding sites in ß(1)389 Arg vs. Gly ARs, which converts α(2C)Del minor allele-associated NE lowering from a therapeutic liability to a benefit. CONCLUSIONS: On combination, the two sets of AR polymorphisms 1) influenced bucindolol efficacy seemingly unpredictably but consistent with their pharmacologic interactions, and 2) identified subpopulations with enhanced (ß(1)389 Arg homozygotes), intermediate (ß(1)389 Gly carriers+α(2C)322-325 Wt homozygotes), and no (ß(1)389 Gly carriers+α(2C)322-325 Del carriers) efficacy.

Post-acute care: the role of natriuretic peptides.

Heart failure is a chronic disease marked by variable acute exacerbations. Once hospitalized the decompensated patient may have signs and symptoms only partially reversed, medical therapy only partially optimized and deranged physiology only partially restored. Therefore, the post-acute care period is one of unique vulnerability and merits efforts of careful and comprehensive assessment of patients at risk of recurrent decompensation and rehospitalization. Natriuretic peptide (NP) assessment which has the ability to monitor dynamic changes in a patient's physiology, may play an important role as part of a post-acute care algorithm focused on early detection and prevention of further decompensation and rehospitalization.

Initial description of cerebral oximetry measurement in heart failure patients.

Cerebral oximetry is a noninvasive technology using near-infrared spectroscopy (NIRS) to monitor regional cerebral tissue oxygen saturation (SctO(2)). NIRS has been widely used for assessing cerebral tissue oxygenation in a variety of populations including the fields of neonatology, anesthesiology, neurology, and cardiac surgery.However, little information has been reported on cerebral oximetry in heart failure (HF) patients. In this observational study, we enrolled 30 patients (15 men) aged 23 to 82 years (mean 67 years) with stage C HF. All patients had New York Heart Association (NYHA) functional class I to III. All patients were on stable HF medical therapy. SctO(2) measurements were recorded from the left and right forehead simultaneously, using FORE-SIGHT cerebral oximeter (CAS Medical Systems Inc, Branford, CT). Feasible associations with SctO(2) risk factors, known to correlate with HF, were recorded. The mean SctO(2) value was 67.4% (range, 47.6%-76.3%), while the mean peripheral tissue saturation (SpO(2)) was 97% (range, 92%-100%). The mean difference between cerebral and peripheral tissue oxygenation (SpO(2)-SctO(2)) was 29.2% (range, 19.2%-51.4%). There was also a significant positive correlation between SctO(2) and mean arterial blood pressure (0.55, P<.01). Statistically significant lower SctO(2) values were observed in patients with diabetes (P=.026; confidence interval [CI], 0.006-0.090) and in patients with dyslipidemia (P=.007; CI, 0.018-0.103). In this initial description of SctO(2) in patients with stage C HF, we noted a wide range of SctO(2) measurements. For most patients, there was a profound SpO(2)-SctO(2) difference, despite near-normal peripheral oxygen saturations. The authors suggest that SctO(2) is a potentially important biomarker to measure in HF patients and may be a useful marker of target organ perfusion.