Management of cardiac diseases in liver transplant recipients: Comprehensive review and multidisciplinary practice-based recommendations.

Cardiac diseases are one of the most common causes of morbidity and mortality following liver transplantation (LT). Prior studies have shown that cardiac diseases affect close to one-third of liver transplant recipients (LTRs) long term and that their incidence has been on the rise. This rise is expected to continue as more patients with advanced age and/or non-alcoholic steatohepatitis undergo LT. In view of the increasing disease burden, a multidisciplinary initiative was developed to critically review the existing literature (between January 1, 1990 and March 17, 2021) surrounding epidemiology, risk assessment, and risk mitigation of coronary heart disease, arrhythmia, heart failure, and valvular heart disease and formulate practice-based recommendations accordingly. In this review, the expert panel emphasizes the importance of optimizing management of metabolic syndrome and its components in LTRs and highlights the cardioprotective potential for the newer diabetes medications (e.g., sodium glucose transporter-2 inhibitors) in this high-risk population. Tailoring the multidisciplinary management of cardiac diseases in LTRs to the cardiometabolic risk profile of the individual patient is critical. The review also outlines numerous knowledge gaps to pave the road for future research in this sphere with the ultimate goal of improving clinical outcomes.

An early relook identifies high-risk trajectories in ambulatory advanced heart failure.

INTRODUCTION: Patients with ambulatory advanced heart failure (HF) are increasingly considered for durable mechanical circulatory support (MCS) and heart transplantation and their effective triage requires careful assessment of the clinical trajectory. METHODS: REVIVAL, a prospective, observational study, enrolled 400 ambulatory advanced HF patients from 21 MCS/transplant centers in 2015-2016. Study design included a clinical re-assessment of Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile within 120 days after enrollment. The prognostic impact of a worsening INTERMACS Profile assigned by the treating physician was assessed at 1 year after the Early Relook. RESULTS: Early Relook was done in 325 of 400 patients (81%), of whom 24% had a worsened INTERMACS Profile, associated with longer HF history and worse baseline INTERMACS profile, but no difference in baseline LVEF (median 0.20), 6-minute walk, quality of life, or other baseline parameters. Early worsening predicted higher rate of the combined primary endpoint of death, urgent MCS, or urgent transplant by 1 year after Early Relook, (28% vs 15%), with hazard ratio 2.2 (95% CI 1.2- 3.8; p = .006) even after adjusting for baseline INTERMACS Profile and Seattle HF Model score. Deterioration to urgent MCS occurred in 14% vs 5% (p = .006) during the year after Early Relook. CONCLUSIONS: Early Relook identifies worsening of INTERMACS Profile in a significant population of ambulatory advanced HF, who had worse outcomes over the subsequent year. Early reassessment of ambulatory advanced HF patients should be performed to better define the trajectory of illness and inform triage to advanced therapies.

Predictive Value of Cardiopulmonary Exercise Testing Parameters in Ambulatory Advanced Heart Failure.

OBJECTIVES: This study sought to determine cardiopulmonary exercise (CPX) predictors of the combined outcome of durable mechanical circulatory support (MCS), transplantation, or death at 1 year among patients with ambulatory advanced heart failure (HF). BACKGROUND: Optimal CPX predictors of outcomes in contemporary ambulatory advanced HF patients are unclear. METHODS: REVIVAL (Registry Evaluation of Vital Information for ventricular assist devices [VADs] in Ambulatory Life) enrolled 400 systolic HF patients, INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles 4-7. CPX was performed by 273 subjects 2 ± 1 months after study enrollment. Discriminative power of maximal (peak oxygen consumption [peak VO2]; VO2 pulse, circulatory power [CP]; peak systolic blood pressure â€¢ peak VO2], peak end-tidal pressure CO2 [PEtCO2], and peak Borg scale score) and submaximal CPX parameters (ventilatory efficiency [VE/VCO2 slope]; VO2 at anaerobic threshold [VO2AT]; and oxygen uptake efficiency slope [OUES]) to predict the composite outcome were assessed by univariate and multivariate Cox regression and Harrell's concordance statistic. RESULTS: At 1 year, there were 39 events (6 transplants, 15 deaths, 18 MCS implantations). Peak VO2, VO2AT, OUES, peak PEtCO2, and CP were higher in the no-event group (all p < 0.001), whereas VE/VCO2 slope was lower (p < 0.0001); respiratory exchange ratio was not different. CP (hazard ratio [HR]: 0.89; p = 0.001), VE/VCO2 slope (HR: 1.05; p = 0.001), and peak Borg scale score (HR: 1.20; p = 0.005) were significant predictors on multivariate analysis (model C-statistic: 0.80). CONCLUSIONS: Among patients with ambulatory advanced HF, the strongest maximal and submaximal CPX predictor of MCS implantation, transplantation, or death at 1 year were CP and VE/VCO2, respectively. The patient-reported measure of exercise effort (Borg scale score) contributed substantially to the prediction of outcomes, a surprising and novel finding that warrants further investigation. (Registry Evaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407).

Assessing the utility of pre-operative first pass radionuclide angiography to predict right ventricular failure post left ventricular assist device implantation.

INTRODUCTION: Right ventricular failure (RVF) after left ventricular assist device (LVAD) placement is associated with worse outcomes. We hypothesized that decreased right ventricular (RV) ejection fraction (EF) as well as qualitative assessments of RV function and dilation, as assessed by first pass radionuclide angiography (FPRNA), are associated with an increased risk of RVF following LVAD implantation. METHODS: We retrospectively identified 46 patients from 1/2008 to 11/2017 that underwent FPRNA and LVAD implantation. RVF was defined as requiring inotropes for greater than 14 days after LVAD implantation or requiring a right ventricular assist device. FPRNA-derived variables of RV performance and structure were compared between those that did and did not have RVF post implant. Statistical analyses were performed with Mann-Whitney U tests for ordinal and continuous variables. Fisher's exact tests and Pearson's χ2 tests were used for categorical variables. RESULTS: Eight patients developed RVF after device implantation. The average RV EF on FPRNA was 41.45% in those that did not develop RVF and 40.13% in those that did (P = 0.787). RV dilation (P = 0.896) and global RV function (P = 0.827) by FPRNA were not statistically different between the two groups. CONCLUSION: In patients that required FPRNA for further assessment of RV function prior to LVAD implantation, decreased RV EF, RV dilation and global RV function on FPRNA were not associated with an increased risk of RVF.

Comorbid Conditions and Health-Related Quality of Life in Ambulatory Heart Failure Patients: REVIVAL (Registry Evaluation of Vital Information for VADs in Ambulatory Life REVIVAL).

BACKGROUND: Patients with heart failure (HF) often have multiple chronic conditions that may impact health-related quality of life (HRQOL) despite HF therapy. We sought to determine the association between noncardiac comorbidities and HRQOL in ambulatory patients with advanced HF. METHODS: Baseline data from 373 subjects in REVIVAL (Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life) were analyzed using multivariable general linear models to evaluate the relationship between comorbidities and HRQOL (EuroQol Visual Analogue Scale, EQ-5D-3L Index Score, and Kansas City Cardiomyopathy Questionnaire). The primary independent variables were a comorbidity index (sum of 14 noncardiac conditions), a residual comorbidity index (without depression), and depression alone. The median (25th to 75th percentile) number of comorbidities was 3 (2-4). RESULTS: Increasing comorbidity burden was associated with a reduction in generic (EQ-5D Index, P=0.005) and HF-specific (Kansas City Cardiomyopathy Questionnaire, P=0.001) HRQOL. The residual comorbidity index was not associated with HRQOL when depression included in the model independently, while depression was associated with HRQOL across all measures. Participants with depression (versus without) scored on average 13 points (95% CI, 8-17) lower on the EuroQol Visual Analogue Scale, 0.15 points (95% CI, 0.12-0.18) lower on the EQ-5D Index, and 24.9 points (95% CI, 21.2-28.5) lower on the Kansas City Cardiomyopathy Questionnaire overall summary score. CONCLUSIONS: While noncardiac comorbidities were prevalent in ambulatory advanced HF patients, only depression was associated with decreased generic and HF-specific HRQOL. Other than depression, the presence of noncardiac comorbidities should not impact expected gains in HRQOL following ventricular assist device implantation, provided the conditions are not a contraindication to implant. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01369407.

Management of heart failure in patients with end-stage kidney disease on maintenance dialysis: a practical guide.

End-stage kidney disease (ESKD) and heart failure (HF) often coexist and must be managed simultaneously. Multidisciplinary collaboration between nephrology and cardiology is critical when treating patients with such complicated physiology. There is no "one-size-fits-all" approach to the evaluation of patients with new left ventricular systolic dysfunction, and diagnostic testing should be adapted to an individual's risk factors. Guideline-directed medical therapy (GDMT) for systolic heart failure should be employed in these patients. While limited randomized data exist, observational data and post hoc analyses suggest that GDMT, including renin angiotensin aldosterone system inhibitors, is associated with improved cardiovascular outcomes and can be safely initiated at low doses with close monitoring of kidney function in this population. Volume status is typically managed through ultrafiltration, so close communication between cardiology and nephrology is necessary to achieve a patient's optimal dry weight and mitigate intradialytic hypotension. Patient education and engagement regarding sodium and fluid restriction is crucial, and symptom burden should be reassessed following changes to the dialysis regimen.

Right ventricular function and residual mitral regurgitation after left ventricular assist device implantation determines the incidence of right heart failure.

BACKGROUND: The effect of significant mitral regurgitation (MR) on outcomes after continuous flow left ventricular assist device (cfLVAD) implantation remains unclear. METHODS: We performed a retrospective review of prospectively collected data from 159 patients with preoperative severe MR who underwent cfLVAD implantation (2003-2017). Two-step cluster analysis using the log-likelihood distance for post-cfLVAD implantation parameters, which included right ventricular (RV) dysfunction, MR severity, and tricuspid regurgitation (TR) severity. Post-cfLVAD implantation echocardiographic parameters were obtained within the first month. RESULTS: Cluster analysis resulted in 3 groups. Group 1 (n = 67) had mild or less MR with moderate-severe RV dysfunction (RVD). Group 2 (n = 43) had moderate-severe MR with moderate-severe RVD. Group 3 (n = 49) had moderate MR with mild RVD. Group 2 had the largest proportion with Interagency Registry for Mechanically Assisted Circulatory Support score of 1 (30.2%) and 2 (41.9%). They were more likely to undergo temporary mechanical circulatory support (18.6%) and tricuspid valve procedure (62.8%). Group 2 had the highest rate of stroke (30.2%; P = .02), hemolysis (39.5%; P = .01), device thrombosis (30%; P = .01), and worst survival (46.5%; P = .01). Survival at 5 years for groups 1, 2, and 3 were 56.0%, 17.6%, and 55.8%. Regression analysis of the entire population showed that greater MR severity after cfLVAD was associated with RV failure (P < .05; odds ratio, 1.6) and RV assist device use (P = .09; odds ratio, 1.6). After excluding tricuspid valve repairs, MR severity had a positive correlation with TR severity (R = 0.33; P < .01). CONCLUSIONS: After cfLVAD implantation, moderate-severe MR and RVD predicted RV failure. Patients with preoperative moderate-severe MR and TR coupled with moderate-severe RVD might benefit the most from mitral and tricuspid valve intervention.

Quality of life and treatment preference for ventricular assist device therapy in ambulatory advanced heart failure: A report from the REVIVAL study.

BACKGROUND: The Registry Evaluation of Vital Information for Ventricular Assist Devices (VADs) in Ambulatory Life study is a prospective multicenter cohort of 400 ambulatory patients with advanced chronic systolic heart failure (HF). The aim of the study is to better understand disease trajectory and optimal timing of advanced HF therapies. We examined patient health-related quality of life (HRQOL) data collected at enrollment and their association with patient treatment preferences for VAD placement. METHODS: Baseline assessment of HRQOL included the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQol EQ-5D-3L Visual Analogue Scale (VAS), along with patient self-assessment of remaining life (PSARL). Descriptive statistics were used to present baseline HRQOL data and Spearman correlation tests to assess the association between KCCQ, VAS, and VAD treatment preference with patient clinical characteristics of interest. RESULTS: The median age was 60 years, 75% were male, and the median left ventricular ejection fraction was 20%. The median (25th percentile, 75th percentile), baseline KCCQ summary score was 64 (48, 78), VAS score 65 (50, 75), and PSARL 7 years (5, 10). There were statistically significant associations of baseline KCCQ and VAS with New York Heart Association class and Interagency Registry of Mechanically Assisted Circulatory Support profile (p < 0.005 for all comparisons). Baseline KCCQ and VAS revealed a modest association with PSARL (correlation = 0.45 and 0.35, respectively; p < 0.001), and many patients were overly optimistic about their expected survival. VAD treatment preference was associated with KCCQ scores (p < 0.031), but the absolute differences were small. VAD treatment preference was independent of other key clinical characteristics such as subject age, VAS, and PSARL. CONCLUSIONS: We found a lack of strong association between HRQOL and patient preference for VAD therapy. Better understanding of patients' perceptions of their illness and how this relates to HRQOL outcomes, clinician risk assessment, and patient decision-making is needed. This may in turn allow better guidance toward available HF therapies in this vulnerable population.

Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL): Rationale, design, baseline characteristics, and inclusion criteria performance.

INTRODUCTION: Improved understanding of the clinical course of ambulatory advanced chronic systolic heart failure may improve the provision of appropriate care and is central to the design of clinical trials in this population. METHODS: Twenty-one implanting ventricular assist device (VAD) centers enrolled 400 subjects in the Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL), a prospective, observational study in ambulatory, chronic, advanced systolic heart failure, designed to identify a cohort with an approximately 25% 1-year risk of the primary composite outcome of death, urgent transplant, or durable mechanical circulatory support. Inclusion criteria utilized only information collected during routine clinical care. Exclusion criteria identified patients with contraindications to VAD. Study inclusion required at least 1 of 10 high-risk criteria derived from established hospitalization and non-hospitalization markers of increased mortality risk. We evaluated the test performance characteristics of the high-risk criteria. RESULTS: Data on 373 subjects evaluable for the primary composite outcome at the 1-year visit are presented. Baseline data were consistent with a less advanced cohort than Medical Arm for Mechanically Assisted Circulatory Support or Risk Assessment (MedaMACS) and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients (ROADMAP). Freedom from the primary composite outcome was 75.9%. Non-hospitalization inclusion criteria identified 89% of patients with events. CONCLUSIONS: Using routinely obtained clinical information for enrollment, REVIVAL successfully recruited an ambulatory chronic systolic heart failure cohort with an approximately 25% annual risk of the primary composite outcome. Information from this registry will be relevant to the planning of future trials of earlier VAD use and of other interventions in this population.

Right ventricular failure following left ventricular assist device implantation is associated with a preoperative pro-inflammatory response.

BACKGROUND: Systemic inflammation during implant of a durable left ventricular assist device (LVAD) may contribute to adverse outcomes. We investigated the association of the preoperative inflammatory markers with subsequent right ventricular failure (RVF). MATERIALS AND METHODS: Prospective data was collected on 489 patients from 2003 through 2017 who underwent implantation of a durable LVAD. Uni- and multivariable correlation with leukocytosis was determined using linear and binary logistic regression. The population was also separated into low (< 10.5 K/ul, n = 362) and high (> 10.5 K/ul, n = 127) white blood cell count (WBC) groups. Mantel-Cox statistics was used to analyze survival data. RESULTS: Postop RVF was associated with a higher preop WBC (11.3 + 5.7 vs 8.7 + 3.1) and C-reactive protein (CRP, 5.6 + 4.4 vs 3.3 + 4.7) levels. Multivariable analysis identified an independent association between increased WBC preoperatively with increased lactate dehydrogenase (LDH, P < 0.001), heart rate (P < 0.001), CRP (P = 0.006), creatinine (P = 0.048), and INR (P = 0.049). The high WBC group was more likely to be on preoperative temporary circulatory support (17.3% vs 6.4%, P < 0.001) with a trend towards greater use of an intra-aortic balloon pump (55.9% vs 47.2%, P = 0.093). The high WBC group had poorer mid-term survival (P = 0.042). CONCLUSIONS: Postop RVF is associated with a preoperative pro-inflammatory environment. This may be secondary to the increased systemic stress of decompensated heart failure. Systemic inflammation in the decompensated heart failure may contribute to RVF after LVAD implant.

Outcomes with ambulatory advanced heart failure from the Medical Arm of Mechanically Assisted Circulatory Support (MedaMACS) Registry.

BACKGROUND: The outlook for ambulatory patients with advanced heart failure (HF) and the appropriate timing for left ventricular assist device (LVAD) or transplant remain uncertain. The aim of this study was to better understand disease trajectory and rates of progression to subsequent LVAD therapy and transplant in ambulatory advanced HF. METHODS: Patients with advanced HF who were New York Heart Association (NYHA) Class III or IV and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 4 to 7, despite optimal medical therapy (without inotropic therapy), were enrolled across 11 centers and followed for the end-points of survival, transplantation, LVAD placement, and health-related quality of life. A secondary intention-to-treat survival analysis compared outcomes for MedaMACS patients with a matched group of Profile 4 to 7 patients with LVADs from the INTERMACS registry. RESULTS: Between May 2013 and October 2015, 161 patients were enrolled with INTERMACS Profiles 4 (12%), 5 (32%), 6 (49%), and 7 (7%). By 2 years after enrollment, 75 (47%) patients had reached a primary end-point with 39 (24%) deaths, 17 (11%) undergoing LVAD implantation, and 19 (12%) receiving a transplant. Compared with 1,753 patients with Profiles 4 to 7 receiving LVAD therapy, there was no overall difference in intention-to-treat survival between medical and LVAD therapy, but survival with LVAD therapy was superior to medical therapy among Profile 4 and 5 patients (p = 0.0092). Baseline health-related quality of life was lower among patients receiving a LVAD than those enrolled on continuing oral medical therapy, but increased after 1 year for survivors in both cohorts. CONCLUSIONS: Ambulatory patients with advanced HF are at high risk for poor outcomes, with only 53% alive on medical therapy after 2 years of follow-up. Survival was similar for medical and LVAD therapy in the overall cohort, which included the lower severity Profiles 6 and 7, but survival was better with LVAD therapy among patients in Profiles 4 and 5. Given the poor outcomes in this group of advanced HF patients, timely consideration of transplant and LVAD is of critical importance.

Cluster analysis of preoperative echocardiographic findings and outcomes following left ventricular device implantation.

OBJECTIVE: To investigate whether preoperative echocardiography findings determine postoperative continuous-flow left ventricular assist device outcomes. METHODS: From January 2003 to June 2017, 490 patients received a durable, continuous-flow left ventricular assist device. Two-step clustering of parameters including heart rate and preoperative echocardiographic findings (ie, left ventricular [LV] ejection fraction, right ventricular [RV] function, aortic insufficiency, mitral regurgitation [MR], tricuspid regurgitation [TR]) was performed and identified 5 distinct clusters associated with LV failure: group 1: moderate right ventricular dysfunction (RVD), severe MR and mild TR (n = 110); group 2: severe RVD, severe MR and TR (n = 64); group 3: moderate RVD and severe aortic insufficiency (n = 16); group 4: mild RVD and mild valvular pathology (n = 163); and group 5: moderate-severe RVD and mild valvular pathology (n = 137). Silhouette measure of cohesion and separation demonstrated satisfactory separation at 0.6. RESULTS: Group 2 had the greatest Interagency Registry for Mechanically Assisted Circulatory Support Level 1 (25%, P = .010), preoperative right atrial pressure (11 ± 5 mm Hg, P < .001), incidence of postoperative right ventricular failure (RVF; 20%, P = .001), delayed closure of the sternum (61%, P = .002), postoperative permanent dialysis (6%, P = .04), rate of tricuspid valve repair (n = 52; 81%, P < .001), and lowest RV stroke work index (489 ± 228 cc mm Hg/m2/beat, P < .001). RVF in groups 1, 3, 4, and 5 was 6%, 0%, 4%, and 9%, respectively. No differences in incidence of heart transplantation (P = .400) or survival (P = .535) were found. Severe TR predicted RVF in those with moderate-severe preoperative RVD (P = .001, odds ratio 3.9). CONCLUSIONS: Clustering demonstrated the importance of preoperative TR in predicting RVF. Combined severe LV and RV failure with severe MR and TR portends the worse prognosis.

Discordant Perceptions of Prognosis and Treatment Options Between Physicians and Patients With Advanced Heart Failure.

OBJECTIVES: This study assessed patient and physician perceptions of heart failure (HF) disease severity and treatment options. BACKGROUND: The prognosis for ambulatory patients with advanced HF on medical therapy is uncertain, yet has important implications for decision making regarding transplantation and left ventricular assist device (LVAD) placement. METHODS: Ambulatory patients with advanced HF (New York Heart Association functional class III to IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4 to 7) on optimized medical therapy were enrolled across 11 centers. At baseline, treating cardiologists rated patients for perceived risk for transplant, LVAD, or death in the upcoming year. Patients were also surveyed about their own perceptions of life expectancy and willingness to undergo various interventions. RESULTS: At enrollment, physicians regarded 111 of 161 patients (69%) of the total cohort to be at high risk for transplant, LVAD, or death, whereas only 23 patients (14%) felt they were at high risk. After a mean follow-up of 13 months, 61 patients (38%) experienced an endpoint of 33 deaths (21%), 13 transplants (8%), and 15 LVAD implants (9%). There was poor discrimination between risk prediction among both patients and physicians. Among physician-identified high-risk patients, 77% described willingness to consider LVAD, but 63% indicated that they would decline 1 or more other simpler forms of life-sustaining therapy such as ventilation, dialysis, or a feeding tube. CONCLUSIONS: Among patients with advanced HF, physicians identified most to be at high risk for transplantation, LVAD, or death, whereas few patients recognized themselves to be at high risk. Patients expressed inconsistent attitudes toward lifesaving treatments, possibly indicating poor understanding of these therapies. Educational interventions regarding disease severity and treatment options should be introduced prior to the need for advanced therapies such as intravenous inotropic therapy, transplantation, or LVAD.

High early event rates in patients with questionable eligibility for advanced heart failure therapies: Results from the Medical Arm of Mechanically Assisted Circulatory Support (Medamacs) Registry.

BACKGROUND: The prognosis of ambulatory patients with advanced heart failure (HF) who are not yet inotrope dependent and implications for evaluation and timing for transplant or destination therapy with a left ventricular assist device (DT-LVAD) are unknown. We hypothesized that the characteristics defining eligibility for advanced HF therapies would be a primary determinant of outcomes in these patients. METHODS: Ambulatory patients with advanced HF (New York Heart Association class III-IV, Interagency Registry for Mechanically Assisted Circulatory Support profiles 4-7) were enrolled across 11 centers from May 2013 to February 2015. Patients were stratified into 3 groups: likely transplant eligible, DT-LVAD eligible, and ineligible for both transplant and DT-LVAD. Clinical characteristics were collected, and patients were prospectively followed for death, transplant, and left ventricular assist device implantation. RESULTS: The study enrolled 144 patients with a mean follow-up of 10 ± 6 months. Patients in the ineligible cohort (n = 43) had worse congestion, renal function, and anemia compared with transplant (n = 51) and DT-LVAD (n = 50) eligible patients. Ineligible patients had higher mortality (23.3% vs 8.0% in DT-LVAD group and 5.9% in transplant group, p = 0.02). The differences in mortality were related to lower rates of transplantation (11.8% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p = 0.02) and left ventricular assist device implantation (15.7% in transplant group vs 2.0% in DT-LVAD group and 0% in ineligible group, p < 0.01). CONCLUSIONS: Ambulatory patients with advanced HF who were deemed ineligible for transplant and DT-LVAD had markers of greater HF severity and a higher rate of mortality compared with patients eligible for transplant or DT-LVAD. The high early event rate in this group emphasizes the need for timely evaluation and decision making regarding lifesaving therapies.

The worst symptom as defined by patients during heart failure hospitalization: implications for response to therapy.

BACKGROUND: Patients perceive different symptoms of heart failure decompensation. It is not known whether the nature of the worst symptom relates to hemodynamic profile, response to therapy, or improvement in clinical trials. METHODS AND RESULTS: Patients in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial were hospitalized with advanced heart failure, ejection fraction ≤30%, and at least 1 sign and 1 symptom of elevated filling pressures. Visual analog scales (VAS) for symptoms were completed by 371 patients, who selected their worst symptom as difficulty breathing, fatigue, abdominal discomfort, or body swelling and also scored breathing and global condition at baseline and discharge. The dominant symptom identified was difficulty breathing by 193 (52%) patients, fatigue by 118 (32%), and abdominal discomfort and swelling each by 30 (8%) patients, combined as right-sided congestion for analysis. Clinical and hemodynamic assessments were not different between groups except that right-sided congestion was associated with more hepatomegaly, ascites, third heart sounds, and jugular venous distention. This group also had greater reduction in jugular venous distention and trend toward higher blood urea nitrogen after therapy. By discharge, average improvements in worst symptom and global score were 28 points and 24 points. For those with ≥10 points in improvement in worst symptom, 84% also improved global assessment ≥10 points. Initial fatigue was associated with less improvement (P = .002) during and after hospitalization, but improvements in symptom scores were sustained when re-measured during 6 months after discharge. CONCLUSION: In most patients hospitalized with clinical congestion, therapy will improve symptoms regardless of the worst symptom perceived, with more evidence of baseline fluid retention and reduction during therapy for worst symptoms of abdominal discomfort or edema. Improvement in trials should be similar when tracking worst symptom, dyspnea, or global assessment.

Mismatch of right- and left-sided filling pressures in chronic heart failure.

BACKGROUND: In patients with advanced heart failure (HF), elevated jugular venous pressure (JVP) is the most reliable sign of elevated left-sided filling pressures. However, discordance between right- and left-sided filling pressures (R-L mismatch) could lead to inadequate or excessive therapy guided by JVP. We determined the prevalence of R-L mismatch in the current era and investigated whether mismatch might be identified from clinical information. METHODS AND RESULTS: Right-sided heart catheterization was performed in 537 consecutive patients hospitalized with advanced HF during complete transplantation evaluation. Patients with high filling pressures were categorized as matched (right atrial pressure (RAP) ≥10 mm Hg and pulmonary wedge pressure (PCWP) ≥22 mm Hg), high-R mismatch (RAP ≥10 but PCWP <22 mm Hg) or high-L mismatch (PCWP ≥22 but RAP <10 mm Hg). Among all of the patients, 195 (36%) were matched low and 194 (36%) were matched high, and 148 (28%) had R-L mismatch. Among patients with high filling pressures, 194 (57%) were matched high and 82 (24%) had high-L and 66 (19%) high-R mismatch. Mismatches were not associated with differences in demographic or clinical data, including pulmonary and hepatic function, or severity of valvular regurgitation and right ventricular function by echo. However, among all patients with RAP ≥10 mm Hg, pulmonary artery systolic pressure (PASP) was higher in those patients with matched high left- and right-sided pressures (59 ± 12 mm Hg) versus high-R mismatch (41 ± 13 mm Hg; P < .0001). Similarly among all patients with low RAP, PASP was lower in patients with matched low right- and left-side pressures (33 ± 11 mm Hg) versus high-L mismatch (53 ± 13 mm Hg; P < .0001). CONCLUSIONS: R-L mismatch was present in >1 in 4 total patients, and >1 in 3 with elevated filling pressures. Regardless of clinical history, when empiric therapy to optimize volume status to JVP is not effective, additional measurement should be considered to establish the R-L relationship.

Right ventricular dysfunction during intensive pharmacologic unloading persists after mechanical unloading.

BACKGROUND: Right ventricular (RV) dysfunction is associated with adverse outcomes in heart failure (HF). Mechanical unloading should be more effective than pharmacologic therapy to reduce RV afterload and improve RV function. We compared RV size and function after aggressive medical unloading therapy to that achieved in the same patients after 3 months of left ventricular assist device (LVAD) support. METHODS AND RESULTS: We studied 20 patients who underwent isolated LVAD placement (9 pulsatile and 11 axial flow). Echocardiograms were performed after inpatient optimization with diuretic and inotropic therapy and compared with studies done after 3 months of LVAD support. After medical optimization right atrial pressure was 11 +/- 5 mm Hg, mean pulmonary artery pressure 36 +/- 11 mm Hg, pulmonary capillary wedge pressure 23 +/- 9 mm Hg, and cardiac index 2.0 +/- 0.6 L.min.m(2). Preoperatively, RV dysfunction was moderate (2.6 +/- 0.9 on a 0 to 4 scale), RV diameter at the base was 3.1 +/- 0.6 cm, and mid-RV was 3.5 +/- 0.6 cm. After median LVAD support of 123 days (92 to 170), RV size and global RV dysfunction (2.6 +/- 0.9) failed to improve, despite reduced RV afterload. CONCLUSIONS: RV dysfunction seen on intensive medical therapy persisted after 3 months of LVAD unloading therapy. Selection of candidates for isolated LV support should anticipate persistence of RV dysfunction observed on inotropic therapy.

Reduction in mitral regurgitation during therapy guided by measured filling pressures in the ESCAPE trial.

BACKGROUND: Dynamic mitral regurgitation (MR) contributes to decompensation in chronic dilated heart failure. Reduction of MR was the primary physiological end point in the ESCAPE trial, which compared acute therapy guided by jugular venous pressure, edema, and weight (CLIN) with therapy guided additionally by pulmonary artery catheters (PAC) toward pulmonary wedge pressure