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.

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.

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.

Understanding the variability in red cell and plasma volume combinations can help guide management in heart failure.

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.

Blood Volume Analysis and Cardiorenal 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: Our objectives encompass a comprehensive understanding of how BVA informs the evaluation and treatment of CRS, including its subtypes, pathophysiology, and clinical significance. We delve into BVA principles, techniques, and measurements, elucidating its diagnostic potential and advantages compared to commonly used surrogate measures. We dissect the clinical relevance of BVA in various CRS scenarios, emphasizing its unique contributions to each subtype. 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. Acknowledging the challenges and limitations associated with BVA's clinical implementation, we underscore the importance of multidisciplinary collaboration among cardiologists, nephrologists, and other clinicians. 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.

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.

Management of anemia in heart failure.

PURPOSE OF REVIEW: Anemia is a relatively common finding in heart failure. Anemia in heart failure patients has been independently associated with reduced exercise tolerance, increased heart failure hospitalizations and increased all-cause mortality. Anemia would appear to be a reasonable treatment target for patients with heart failure. The review will discuss the potential causes of anemia in heart failure patients and give an up-to-date overview of treatment trials. RECENT FINDINGS: Studies assessing the pathophysiology of anemia in heart failure patients have recently demonstrated the potential importance of iron deficiency, abnormal iron metabolism and hemodilution. Treatment studies have focused on the use of erythropoiesis-stimulating agents, with recent trials showing mixed results. SUMMARY: Despite initial studies indicating a possible beneficial effect of erythropoiesis-stimulating agents in the treatment of anemic heart failure patients, clinical trial data, to date, have failed to show convincing evidence for morbidity or mortality benefit, and information on the long-term safety is lacking. Ongoing large-scale trials will have the potential to provide such information in the future.

Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: implications for patient selection.

BACKGROUND: The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial first demonstrated that implantation of left ventricular assist devices (LVADs) as destination therapy (DT) can provide survival superior to any known medical treatment in patients with end-stage heart failure who are ineligible for transplantation. In the present study, we describe outcomes of DT in the post-REMATCH era in the United States. METHODS AND RESULTS: The present study included 280 patients who underwent HeartMate XVE LVAD implantation between November 2001 and December 2005. A preoperative risk score for in-hospital mortality after LVAD implantation was established in 222 patients with complete data. All patients were followed up until death or December 2006. The 1-year survival after LVAD implantation was 56%. The in-hospital mortality after LVAD surgery was 27%. The main causes of death included sepsis, right heart failure, and multiorgan failure. The most important determinants of in-hospital mortality were poor nutrition, hematological abnormalities, markers of end-organ or right ventricular dysfunction, and lack of inotropic support. Stratification of DT candidates into low (n=65), medium (n=111), high (n=28), and very high (n=18) risk on the basis of the risk score calculated from these predictors corresponded with 1-year survival rates of 81%, 62%, 28%, and 11%, respectively. CONCLUSIONS: Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Patients with advanced heart failure who are referred for DT before major complications of heart failure develop have the best chance of achieving an excellent 1-year survival with LVAD therapy.

Thermal therapy: a viable adjunct in the treatment of heart failure?

The aim of this work was to review and provide a summary of published literature on the clinical impact of thermal therapy (ie, warm water immersion, traditional sauna bathing, and dry infrared sauna) in patients with heart failure. Medline and Embase database literature searches were conducted, and studies that included measurement of heart failure-related clinical parameters were reviewed. Thermal therapy was found to have a positive impact on key heart failure-related parameters across multiple studies. Significant improvements were noted across a wide scope of heart failure-related parameters in the areas of (1) endothelial function, (2) hemodynamics, (3) cardiac geometry, (4) neurohormonal markers, and (5) quality of life. Of special note, thermal therapy also conveyed a strong antiarrhythmic effect in heart failure patients. The clinical evidence highlights repeatable and compelling data showing that thermal therapy may provide an important and viable adjunct in the treatment of heart failure.

Low incidence of neurologic events during long-term support with the HeartMate XVE left ventricular assist device.

Neurologic events during left ventricular assist device (LVAD) support are associated with significant morbidity and death. To evaluate this problem, we analyzed neurocognitive function and the frequency and incidence of neurologic events in 21 consecutive patients who were undergoing long-term support with the HeartMate XVE LVAD (Thoratec Corporation; Pleasanton, Calif). The mean duration of LVAD support was 531 days (range, 55-1, 309 d); the cumulative support time was 11,188 days (30.7 yr). No patients received anticoagulant therapy, and most received aspirin. None experienced strokes or transient ischemic attacks. Twenty patients were discharged from the hospital; 2 were later readmitted because of transient changes in neurologic status (metabolic encephalopathy) that ultimately resolved. Neurologic function, as measured by the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Score (MRS), was abnormal before LVAD implantation but normal 6 and 12 months after (mean NIHSS, 23.6 before vs 0 after; mean MRS, 0.68 before vs 0.18 after). Neurocognitive function, as evaluated by the Boston Naming Test, Trail Making Test part B, and Block Design Test, also improved during LVAD support. Together, these findings indicate that few neurologic events occur during long-term HeartMate XVE LVAD support in the absence of anticoagulation therapy. They also suggest that modifications made to the HeartMate LVAD since the REMATCH trial have resulted in fewer complications, and that better patient selection and supportive care have improved outcomes.

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.

The Second Follow-up Serial Infusions of Nesiritide (FUSION II) trial for advanced heart failure: study rationale and design.

BACKGROUND: Patients with persistently symptomatic advanced heart failure have limited treatment options after appropriate use of standard evidence-based therapies. Current recommendations from the American College of Cardiology/American Heart Association guidelines for treatment of stage C/D heart failure beyond standard therapy include ventricular replacement, investigational agents, and palliative interventions. Given the elevated risk of this patient population, additional treatment options seem warranted. Natriuretic peptides are protean compounds that provoke vasodilation, natriuresis, neurohormonal antagonism, and reverse remodeling, but they have an uncertain risk-benefit profile affecting serum creatinine and clinical events. In the pilot, open-label FUSION I trial, the adjunctive administration of nesiritide with standard therapy for patients with advanced heart failure, was demonstrated to have a neutral effect on outcomes with no evidence of increased risk. Within a prespecified subset of high-risk patients, a potential signal of benefit on a combined end point of mortality and cardiovascular hospitalization was identified. STUDY DESIGN: FUSION II is a 900-patient randomized, placebo-controlled, double-blind, phase IIb trial designed to further assess the safety, efficacy, and optimal dosing frequency of outpatient nesiritide for advanced heart failure. The primary end point is a composite of all-cause mortality and cardiorenal hospitalization. CONCLUSIONS: If a confirmatory signal of benefit is identified in FUSION II, a definitive phase III mortality/quality of life trial will be warranted. Additional issues related to the influence of disease management, the logistics of outpatient parenteral therapy administration, and future iterations of natriuretic peptide therapy will need to be investigated.

Heat therapy in the management of heart failure.

Heart failure remains a health care epidemic, and additional complementary therapies beyond pharmaceuticals and devices are needed. Using heat therapy or topical thermal therapy is an ancient therapeutic approach for the treatment of heart failure. Currently, there are several studies reporting salutary effects of heat therapy in patients with heart failure using either dry heat or water immersion therapies. The authors describe an additional theoretic construct using topically applied heat pads that might be a simple and economic approach to affect heat therapy as an adjunct for many patients. Hopefully future studies will continue to explore heat therapy as adjunctive care for heart failure patients.

Impact of body mass index on outcomes of enhanced external counterpulsation therapy.

OBJECTIVES: We evaluated the association of baseline body mass index (BMI) on the outcomes of enhanced external counterpulsation (EECP) therapy for chronic stable angina. BACKGROUND: We are in the midst of a pandemic of obesity, which is complicating the care of patients with coronary artery disease (CAD). METHODS: We examined 2730 patients enrolled from 2002 to 2004 in the IEPR-2. Baseline and outcome variables were stratified by the entry BMI in kilograms per meter squared. RESULTS: Obesity (BMI > 30 kg/m2) was common (40.6%) among patients with severe CAD referred for EECP. Within the total cohort, 2.6% was underweight (BMI < or = 20 kg/m2) and 4.5% was morbidly obese (BMI > 40 kg/m2). Prevalence of diabetes, hypertension, dyslipidemia, and heart failure (HF) was higher in obese patients. However, the rates of baseline angina and prior revascularization were similar among the groups. The peak diastolic augmentation ratio was similar between groups during the first (0.7 +/- 0.4 for lowest and highest BMI) and last hours of treatment (0.9 +/- 0.5 and 0.8 +/- 0.5). The cumulative hours of treatment, the change in angina class, and the Duke Activity Status Index were similar for all BMI groups. There was a greater reduction in weekly anginal episodes from baseline across ascending levels of BMI (-6.3 +/- 13.6 to -9.7 +/- 15.8, P = .03). The rates of discontinuation for clinical events were highest (14.3%) with skin breakdown being the most frequent cause (10.1%) in the underweight. The rates of clinical events including myocardial infarction, HF, and death trended higher across ascending levels of BMI (P = .52). Multivariate analysis found that older age, history of stroke, history of HF, and diabetes, but not BMI, were predictors of clinical events. CONCLUSIONS: More than 40% of patients with severe CAD referred for EECP were obese. Underweight patients had higher rates of discontinuation of treatment mainly because of skin breakdown. Symptomatic benefit of EECP was similar among all BMI groups. However, despite symptomatic improvement, there was a nonsignificant trend for higher rates of myocardial infarction, HF, and death as BMI increased.

Acute and chronic oral magnesium supplementation: effects on endothelial function, exercise capacity, and quality of life in patients with symptomatic heart failure.

Endothelial dysfunction is an important pathophysiologic mechanism in the progression of heart failure. The objective of the present study was to determine the effects of acute and chronic oral magnesium supplementation on endothelial function in patients with symptomatic heart failure. Twenty-two symptomatic chronic heart failure patients were randomized to receive 800 mg oral magnesium oxide daily or placebo for 3 months. Data collected included large and small arterial elasticity/compliance, hemodynamic parameters, exercise capacity, and quality-of-life score at baseline, 1 week, and 3 months. Patients who received magnesium had improved small arterial compliance at 3 months from baseline compared with placebo. This study suggests that chronic supplementation with oral magnesium is well tolerated and could improve endothelial function in symptomatic heart failure patients.

Optimizing treatment and outcomes in acute heart failure: beyond initial triage.

Heart failure contributes substantially to health care costs in the United States due to its prevalence and frequent necessity for repeat hospitalizations to manage episodes of acute decompensation. Heart failure overwhelmingly impacts Medicare costs, as the highest proportion of heart failure patients are older than 65 years of age. Efforts to reduce morbidity, mortality, and health care resource utilization have been achieved successfully through emergency department-based heart failure observation units. For select patients, the observation unit can provide care with effective oral agents, including angiotensin-converting enzyme inhibitors, beta-adrenergic receptor blockers, and diuretics, as well as administration of other vasoactive agents, followed by a discharge plan of effective heart failure education and rigorous follow-up management. As advanced pharmacologic and diagnostic therapies continue to emerge, the observation unit staff can play an integral role in the critical education and self-management tools that are needed by the patient to ultimately improve outcomes and quality of life.

Enhanced external counterpulsation improves exercise duration and peak oxygen consumption in older patients with heart failure: a subgroup analysis of the PEECH trial.

The Prospective Evaluation of Enhanced External Counterpulsation in Congestive Heart Failure (PEECH) trial demonstrated that enhanced external counterpulsation (EECP) therapy increased exercise duration and improved functional status and quality of life without affecting peak oxygen consumption. The authors present data from a prespecified subgroup of elderly patients (65 years or older) enrolled in the PEECH trial. The 2 co-primary end points were the percentage of subjects with a >60-second increase in exercise duration and the percentage of subjects with a >1.25-mL/kg/min increase in peak volume of oxygen consumption. At 6-month follow-up, the exercise responder rate was significantly higher in EECP patients compared with controls (P=.008). Further, in contrast to the overall PEECH study, the EECP group demonstrated a significantly higher responder rate for peak oxygen consumption (P=.017). The authors conclude that an older subgroup of PEECH subjects confirms the beneficial effect of EECP in patients with chronic, stable, mild-to-moderate heart failure.