Advanced Heart Failure Therapies Research Articles

Derivation and validation of a multicenter model to identify candidates for advanced HF therapies with high potential to achieve post-LVAD reverse cardiac remodeling

Abstract Background A subset of advanced heart failure (HF) patients can experience significant improvement in their cardiac structure and function while on left ventricular assist device (LVAD) support, which is among the prerequisites for LVAD weaning. Purpose We sought to develop and validate a predictive personalized tool to identify candidates for advanced HF therapies with a high potential to achieve significant improvement in myocardial structure and function post-LVAD. This tool can aid clinicians and patients considering advanced HF therapies options. Methods A total of 884 consecutive LVAD patients were enrolled. The derivation and validation cohorts included 509 patients (from three institutions) and 375 patients from another four institutions), respectively. The primary outcome was "significant reverse remodeling", defined as left ventricular ejection fraction (LVEF) ≥40% and LV end-diastolic diameter ≤6 cm within one year on LVAD support. Bootstrap imputation and LASSO variable selection were used to derive a predictive model which was externally validated. Results Patients were predominantly white (78%), male (80.1%), 57±14 years old. Overall, 12.8% patients were identified as responders. Four variables associated with reverse remodeling were included in the multivariable model achieving a C-statistic of 0.72 (95% CI: 0.66-0.79) in the derivation and 0.75 (95% CI: 0.67-0.84) in the validation cohort (Figure). We created a calculator for individualized prediction of the probability of cardiac recovery and when applied to the studied population, we identified patients with 0.2%-67.6% chance of significant reverse remodeling (see Figure for patient example). Conclusions The Multicenter Recovery Calculator is a predictive tool that provides individualized probability of significant reverse remodeling. This tool may help clinicians and patients to maximize the benefits of both heart transplant and LVAD. Specifically, it may serve to (a) improve patient selection for LVAD as bridge to recovery and (b) benefit transplant waitlist outcomes by prioritizing allocation of donor allografts to patients without a high potential for cardiac reverse remodeling.

Long-term clinical outcomes and patterns of follow-up after cardiogenic shock: insights from an advanced heart failure referral center registry

Abstract Background Inpatient mortality of patients with cardiogenic (CS) has been reported as high as 50%. Those who present in CS are at high risk of having recurrent admissions to hospital or requiring advanced heart failure (HF) therapies. The Toronto General Hospital (TGH) is a quaternary cardiac center, providing mechanical circulatory support (MCS) and heart transplantation (HT), serving as a regional CS transfer hub for a population of over 8 million people. While inpatient management of CS patients has been studied extensively, there is little data on where or how these patients are followed after their discharge. We aimed to determine the long-term clinical outcomes and nature of follow up after a CS admission. Methods This was a retrospective cohort study of CS patients admitted to TGH between 2014 and 2023. We collected data regarding survival to discharge and the type of follow up patients received after their index CS admission. Survival was compared using Kaplan-Meier methods. Results 1582 patients were admitted during the study. The mean age was 59.9 + 16.1 years, including 474 (30.0%) females and 335 (21.2%) patients with acute myocardial infarction CS. In-hospital mortality was 32.4%, with a further 17 (1.8%) patients transferred to palliative care during their index CS admission. After excluding patients who underwent heart transplantation (HT) or durable MCS implant, 679 patients were discharged alive, with median follow-up of the 307 (range 0 – 3436) days. Overall mortality was 57.0%. Among discharged patients, 396 (56.8%) were followed at the regional hub hospital. A further 54 (8.0%) patients were followed by a cardiology provider at a referring community center. A total of 202 (29.7%) patients did not have outpatient follow up arranged at the time of their discharge and no details of further care were available. Median survival during follow-up was higher among patients with confirmed follow-up at the time of their discharge, but not statistically significant (1798 vs 1775 days, p=0.067). There was a significant survival benefit among CS patients followed at a heart function clinic compared with those who were not, (1821 vs. 1775 days, p= 0.020). In terms of candidacy for advanced therapies, having outpatient follow up was associated with receiving durable MCS or HT (6.3% vs. 0.5%, p=0.003). Conclusion Despite advances in the management of CS, overall mortality remains high at 57.0%. Follow-up after CS admission is of essential importance- both in improvement of long-term outcomes, and access to advanced heart failure therapies. There was a survival benefit among patients who were followed in a specialized heart function clinic. Additionally, having outpatient follow up was significantly associated with receiving advanced therapies. Further research is needed to identify the barriers to accessing post discharge follow-up care.

Outcomes of implantable cardioverter-defibrillators in patients with a left ventricular assist device: a systematic review and meta-analysis

Abstract Introduction Implantable Cardioverter-Defibrillators (ICDs) improve survival in advanced heart failure with reduced ejection fraction (HFrEF) and prevent sudden cardiac death. However, the prognostic benefits of ICDs among patients with a Left Ventricular Assist Device (LVAD) remain uncertain and controversial. Therefore, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of ICD implantation among LVAD recipients. Methods We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the peer-reviewed articles published in English assessing the impact of ICD implantation among LVAD recipients, till 10/01/2024. ICD implantation was defined as implantation before LVAD, simultaneous implantation with LVAD, or within 30 days of LVAD insertion. Two independent review authors assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data in forest plots. The primary outcome was all-cause mortality associated with ICD implantation compared to no ICD implantation, and the secondary outcomes included ventricular arrhythmia (VT), and hemorrhagic stroke. Heterogeneity was assessed using Q test and I2, with I2 > 50% indicating marked heterogeneity. Results A total of 13 observational studies comprising 54571 recipients of LVAD were included in the analysis of the primary outcome. All-cause mortality was similar among patients with ICD versus no ICD (Odds Ratio [OR]= 0.77; 95% CI, 0.57-1.04, I2= 89%, P=0.09), as shown in Figure 1. Likewise, ICD implantation was associated with similar rates of VT and hemorrhagic stroke (VT: OR= 1.81, 95% Cl, 0.82-4.01, I2= 90%, P=0.14; hemorrhagic stroke: OR= 1.01, 95% Cl, 0.81-1.25, I2= 0%, P= 0.95). Conclusion Among patients with HFrEF and LVAD as advanced heart failure therapy, ICD implantation didn’t provide additional prognostic survival benefit, suggesting possible use of LVAD without ICD implantation.Figure 1.Forest plot of mortality

Comparative analysis of multi-organ failure trajectories reflected by the MELD-3.0 following heart transplantation and heartmate 3 implantation

Abstract Background Multi-organ failure (MOF) frequently complicates advanced heart failure (HF), substantially impacting patient prognosis. The Model of End-Stage Liver Disease 3.0 (MELD-3.0) scale, encompassing liver and kidney function parameters, is a valuable tool for assessing the severity of organ dysfunction. Purpose This study aims to elucidate the trajectory of MOF in individuals undergoing either heart transplantation (HTx) or left ventricular assist device (LVAD) - HeartMate 3 implantation, utilizing the MELD-3.0 scale, over a 1-year follow-up period. Methods A comprehensive analysis was conducted, examining data from 1 month preceding to 1 year subsequent to the HTx or LVAD implantation. The MELD-3.0 score was calculated using the average values of international normalized ratio, bilirubin, creatinine, sodium, and albumin levels during this timeframe. Comparative assessments of the average MELD-3.0 scores were performed between the HTx and LVAD groups at 1 month pre-procedure, as well as at 1 week, 1 month, 3 months, 6 months, and 1 year post-procedure. Results The analysis included 107 patients undergoing HTx and 31 patients undergoing HMi, with a median age of 54 years (47-62), 85% were male. There was no difference in MELD-3.0 between HTx and LVAD patients in the pre-procedure period: 12.3 (7.3-15.9) vs 13.1 (7.7-16.6), p=0.95. There was also no difference in MELD-3.0 at 1 week and 1 month post-procedure. However, in the 3rd month, the difference gained statistical significance: 7.3 (4.6-9.4) vs 13.8 (11.5-19.7), p<0.01 and continued to be significant in the next follow-ups: 12-month 5.4 (3.1-10.2) vs 11.1 (6.7—15.1), p<0.01, comparing respectively HTx vs LVAD. In both groups of patients, a significant decrease in MELD-3.0 score from 3-month follow-up when compared to 1 month preceding the procedure was observed. Within 12 months post-procedure, 30 patients (22%) died (19 in HTx group and 11 in LVAD group), 8 LVAD patients (26%) had HTx. Conclusion The utilization of the MELD-3.0 scale reveals significant differences in the trajectory of multi-organ failure between HTx and LVAD patients. Both forms of advanced HF therapy result in an improvement of liver and kidney condition, while HTx patients' benefits are larger and last longer, highlighting the distinct impacts of this intervention on organ function.MELD 3.0 score in time

Long-term outcomes of cardiogenic shock survivors: a contemporary retrospective analysis from a tertiary center

Abstract Background Cardiogenic shock (CS) is a complex syndrome that still portends a dismal short-term prognosis. However, in patients that survive the initial admission and are later discharged, the long-term prognosis remains ill-characterized. Aim We aimed to describe the long-term morbidity and mortality outcomes of patients surviving the index admission for CS. Methods Retrospective analysis of all consecutive patients admitted to a cardiac intensive care unit (CICU) between December 2016 and December 2022 with a diagnosis of CS. All etiologies were included and further categorized as: acute myocardial infarction (AMI-CS), acute-on-chronic heart failure (HF-CS) and secondary causes [(S-CS): myocarditis, arrhythmic storm, acute pulmonary embolism, among others]. Our primary endpoint was defined as all-cause death, conditional to being discharged alive. Secondary endpoints comprised heart transplant, durable left ventricular assist device (LVAD) implantation, implantable cardioverter-defibrillator (ICD) insertion and hospital readmission during follow-up. Results A total of 208 patients were included [median age 68 years (IQR 57-80), 66% males, mean Charlson comorbidity index 4±3], of whom 52% (n=108) had AMI-CS, 27% (n=56) HF-CS and 21% (n=44) S-CS. During the index admission, mean SAPS II score was 49±18 and most patients were in SCAI-C (66%, n=137) stage. Organ support in the form of invasive mechanical ventilation, renal replacement therapy or temporary mechanical circulatory assist devices was necessary in 62% (n=129), 27% (n=56) and 26% (n=55) of patients, respectively. 53% of patients (n=110) survived the index admission [median CICU length of stay 8 (IQR 3-15) days; median hospital length of stay 13 (IQR 4-25) days]. At discharge, mean left ventricular ejection fraction was 38±16% and 28% (n=26) of patients underwent ICD implantation. Median follow-up after discharge was 679 (IQR 373-1056) days, with 4 (4%) patients lost to follow-up. Overall mortality was 22% (n=24) and was numerically higher for AMI-CS when compared to HF-CS and S-CS (9% vs 7% vs 6% respectively, p=0.640). Secondary endpoint analysis showed that 10% (n=11) had a heart transplant, 2% (n=2) received a durable LVAD, 9% (n=10) received an ICD and 26% (n=28) were re-hospitalized during that period. Conclusions Although the long-term mortality of patients discharged alive after the index admission for CS is not overwhelming, one in every four will be readmitted and a small proportion will be eligible for advanced heart failure therapies. Healthcare strategies to improve the morbidity and mortality of many CS survivors should be devised.

Trajectories following Impella 5.5 support are associated with initial presentation acuity.

Impella 5.5 is a temporary left ventricular assist device utilized to support patients with cardiogenic shock and those undergoing high-risk cardiac interventions. From October 2019 to January 2023, 226 patients received Impella 5.5 support at Cleveland Clinic main campus. Patients were stratified by Society for Cardiovascular Angiography and Interventions (SCAI) shock stages. Immediate post-Impella 5.5 trajectories were compared across groups. Trajectories were defined as mortality on Impella 5.5, transition to advanced heart failure therapies (durable left ventricular assist device/heart transplantation), or survival to Impella 5.5 removal without advanced therapies. Overall, 148 (65%) patients with cardiogenic shock and 78 (35%) undergoing high-risk cardiac interventions received Impella 5.5 support. SCAI stage was A in 63 (28%), B in 10 (4.4%), C in 29 (13%), D in 104 (46%), and E in 20 (8.8%). Mortality on Impella 5.5 was highest in SCAI stage E (A: 3.2%, B: 10%, C: 14%, D: 27%, E: 35%; p < 0.01). Transition to advanced therapies (durable left ventricular assist device or heart transplantation) was highest in SCAI stages C-D (A: 1.6%, B: 0.0%, C: 45%, D: 36%, E: 20%; p < 0.01). Survival to Impella removal without advanced therapies was highest in SCAI stages A-B (A: 95%, B: 90%, C: 41%, D: 38%, E: 45%; p < 0.01). Stratification by presentation acuity in candidates for Impella 5.5 insertion may help identify which patients may and may not benefit from this escalation of tailored temporary mechanical circulatory support.

Baroreflex activation therapy in advanced heart failure: A long-term follow-up.

Baroreceptor activation therapy (BAT) is a promising new treatment strategy for patients with heart failure with reduced ejection fraction (HFrEF). It provides symptomatic relief, improvement in left ventricular function and reduction of cardiac biomarkers. Data regarding the long-term effect of BAT on HFrEF are scarce. This retrospective, monocentric study aimed to assess long-term outcome in patients who underwent BAT. Patients with HFrEF who received BAT at Hannover Medical School between 2014 and 2023 were followed until the latest available follow-up. Symptom burden, echocardiography and laboratory testing were assessed before BAT implantation and in subsequent follow-ups. Twenty-three patients (mean age 66±10years, 83% male) with HFrEF were included in the study. Aetiology of heart failure was ischaemic in 70%. The majority of patients (96%) suffered from New York Heart Association (NYHA) III with a mean left ventricular ejection fraction (LVEF) of 23±8% and N-terminal pro-B-type natriuretic peptide (NT-proBNP) of 2463±2922pg/mL. A complication occurred in one patient during BAT implantation (4%). The mean follow-up was 3±2 (max. 7.5) years. BAT reduced NYHA classification in 12 patients (52%) after 1year, of which one patient remained in ameliorated NYHA for 7.5years. Echocardiographic evaluation revealed significant improvement in LVEF by 9±9% after 1year (P<0.001) and by 11±9% (P=0.005) after 2years. In addition, BAT mildly reduced NT-proBNP in the first 2years [non-significantly after 1year by 396±1006pg/mL and significantly after 2years by 566±651pg/mL (P=0.039)]. Seven patients reaching the recommended replacement time underwent device exchange. Four patients died during observation time. BAT resulted in a substantial reduction in NYHA classification and improvement in LVEF that lasted over long-term follow-up in many patients. NT-proBNP level decreased interim in long-term follow-up. These findings highlight the long-term efficacy and potential benefits of BAT as a therapeutic intervention for patients with HFrEF.

The relation between socioeconomic status and invasive haemodynamics at evaluation for advanced heart failure.

Socioeconomic deprivation is a risk marker for worse prognosis in patients with heart failure (HF), and a potential barrier to referral for advanced HF evaluation. The relationship between socioeconomic status (SES) and invasive haemodynamics in patients undergoing evaluation for advanced HF therapies is unknown. We combined a consecutive clinical registry of patients evaluated for advanced HF with patient-level data on SES (household income, education, workforce status, cohabitant status and distance from home to tertiary HF centre) derived from nationwide registries. Using this information, the cohort was divided into groups of low-, medium- and high degree of socioeconomic deprivation. The associations between SES and invasive haemodynamics were explored with multiple linear regression adjusted for age and sex. A total of 631 patients were included. The median age was 53years, and 23% were women. Patients in the highest income quartile versus the lowest (Q4 vs. Q1) were older (median age 57 vs. 50years) and more often male (83% vs. 67%), both P<0.001. Increasing household income (per 100000 Danish kroner,1 EUR=7.4 DKK) was associated with lower pulmonary capillary wedge pressure (PCWP)[-0.18mmHg, 95% confidence interval (CI) -0.36 to -0.01, P=0.036] but not significantly associated with central venous pressure (CVP) (-0.07mmHg, 95% CI -0.21 to 0.06, P=0.27), cardiac index (-0.004L/min/m2, 95% CI -0.02 to 0.01, P=0.60), or pulmonary vascular resistance (PVR) (-0.003 Wood units, 95% CI -0.37 to 0.16, P=0.84). Comparing the most deprived with the least deprived group, adjusted mean PVR was higher (0.35 Wood units, 95% CI 0.02 to 0.68, P=0.04), but PCWP (0.66mmHg, 95% CI -1.49 to 2.82, P=0.55), CVP (-0.26mmHg, 95% CI -1.76 to 1.24, P=0.73) and cardiac index (-0.03L/min/m2, 95% CI -0.22 to 0.17, P=0.78) were similar. Most haemodynamic measurements were similar across layers of SES. Nevertheless, there were some indications of worse haemodynamics in patients with lower household income or a high accumulated burden of socioeconomic deprivation. Particular attention may be warranted in socioeconomically deprived patients to ensure timely referral for advanced HF evaluation.

Socio-economic inequalities and heart failure morbidity and mortality: A systematic review and data synthesis.

Socio-economic status (SES) has been associated with incident and prevalent heart failure (HF), as well as its morbidity and mortality. However, the precise nature of the relationship between SES and HF remains unclear due to inconsistent data. This study aims to provide a comprehensive assessment and data synthesis of the relationship between SES and HF morbidity and mortality. We performed a systematic search and data synthesis using six databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. The included studies comprised observational studies that reported on HF incidence and prevalence, HF hospitalizations, worsening HF (WHF) and all-cause mortality, as well as treatment options (medical, device and advanced HF therapies). SES was measured on both individual and area levels, encompassing single (e.g., income, education, employment, social risk score, living conditions and housing characteristics) and composite indicators. Among the 4124 studies screened, 79 were included, with an additional 5 identified through cross-referencing. In the majority of studies, a low SES was associated with an increased HF incidence (72%) and prevalence (75%). For mortality, we demonstrated that low SES was associated with increased mortality in 45% of the studies, with 18% of the studies showing mixed results (depending on the indicator, gender or follow-up) and 38% showing non-significant results. Similar patterns were observed for the association between SES, WHF, medical therapy prescriptions and the utilization of devices and advanced HF therapies. There was no clear pattern in the used SES indicators and HF outcomes. This systematic review, using contemporary data, shows that while socio-economic disparity may influence HF incidence, management and subsequent adverse events, these associations are not uniformly predictive. Our review highlights that the impact of SES varies depending on the specific indicators used, reflecting the complexity of its influence on health disparities. Assessment and recognition of SES as an important risk factor can assist clinicians in early detection and customizing HF treatment, while also aiding policymakers in optimizing resource allocation.

Evaluation and Management of Kidney Dysfunction in Advanced Heart Failure: A Scientific Statement From the American Heart Association.

Early identification of kidney dysfunction in patients with advanced heart failure is crucial for timely interventions. In addition to elevations in serum creatinine, kidney dysfunction encompasses inadequate maintenance of sodium and volume homeostasis, retention of uremic solutes, and disrupted endocrine functions. Hemodynamic derangements and maladaptive neurohormonal upregulations contribute to fluctuations in kidney indices and electrolytes that may recover with guideline-directed medical therapy. Quantifying the extent of underlying irreversible intrinsic kidney disease is crucial in predicting whether optimization of congestion and guideline-directed medical therapy can stabilize kidney function. This scientific statement focuses on clinical management of patients experiencing kidney dysfunction through the trajectory of advanced heart failure, with specific focus on (1) the conceptual framework for appropriate evaluation of kidney dysfunction within the context of clinical trajectories in advanced heart failure, including in the consideration of advanced heart failure therapies; (2) preoperative, perioperative, and postoperative approaches to evaluation and management of kidney disease for advanced surgical therapies (durable left ventricular assist device/heart transplantation) and kidney replacement therapies; and (3) the key concepts in palliative care and decision-making processes unique to individuals with concomitant advanced heart failure and kidney disease.

Short term outcomes and resource utilization in de-novo versus acute on chronic heart failure related cardiogenic shock: a nationwide analysis.

There has been growing recognition of non-ischemic etiologies of cardiogenic shock (CS). To further understand this population, we aimed to investigate differences in clinical course between acute on chronic heart failure related (CHF-CS) and de-novo CS (DN-CS). Using the Nationwide Readmission Database, we examined 92,426 CS cases. Outcomes of interest included in-hospital and 30-day outcomes and use of advanced heart failure therapies. Patients with DN-CS had higher in-hospital mortality than the CHF-CS cohort (32.6% vs. 30.4%, p < 0.001). Mechanical circulatory support (11.9% vs. 8.6%, p < 0.001) was more utilized in DN-CS. Renal replacement therapy (13.8% vs. 15.5%, p < 0.001) and right heart catheterization (16.0% vs. 21.0%, p < 0.001) were implemented more in the CHF-CS cohort. The CHF-CS cohort was also more likely to undergo LVAD implantation (0.4% vs. 3.6%, p < 0.001) and heart transplantation (0.5% vs. 2.0%, p < 0.001). Over the study period, advanced heart failure therapy utilization increased, but the proportion of patients receiving these interventions remained unchanged. Thirty days after index hospitalization, the CHF-CS cohort had more readmissions for heart failure (1.1% vs. 2.4%, p < 0.001) and all causes (14.1% vs. 21.1%, p < 0.001) with higher readmission mortality (1.1% vs. 2.3%, p < 0.001). Our findings align with existing research, demonstrating higher in-hospital mortality in the DN-CS subgroup. After the index hospitalization, however, the CHF-CS cohort performed worse with higher all-cause readmission rate and readmission mortality. The study also underscores the need for further investigation into the underutilization of certain interventions and the observed trends in the management of these CS subgroups.

Clinical Outcomes and Left Ventricular Functional Remodeling after Extracorporeal Membrane Oxygenation Assisted Percutaneous Coronary Intervention in Patients with Ischemic Cardiomyopathy: A Single-Center Retrospective Observational Study of 76 Cases.

Ischemic cardiomyopathy (ICM) is a common condition that leads to left ventricular (LV) functional remodeling and poor prognosis. Extracorporeal membrane oxygenation (ECMO) can provide temporary circulatory support and facilitate percutaneous coronary intervention (PCI) in patients with ICM and hemodynamic instability. However, the impact of ECMO-assisted PCI on LV functional remodeling and clinical outcomes in ICM patients is unclear. We retrospectively analyzed 76 patients with ICM who underwent ECMO-assisted PCI at our institution between January 2013 and December 2022. We assessed the changes in LV functional remodeling using echocardiography at baseline and 12 months after the procedure. We also evaluated the incidence of major adverse cardiac and cerebrovascular events (MACCEs) and ECMO-related complications during hospitalization and at one-year follow-up. The mean baseline left ventricular ejection fraction (LVEF) was 29.98 ± 2.65%. The rate of complete revascularization was 58%. The median duration of ECMO support was 38.99 hours. The most common ECMO-related complications were bleeding (8%) and lower extremity ischemia (5%). The one-year mortality rate was 30%. The overall freedom from MACCEs at 12 months was 59% (95% confidence interval (CI): 49-71%). LVEF increased significantly after the procedure from baseline to 6 months, yet decreased slightly at 12 months, although it was still higher than the baseline value. Wall motion score index (WMSI), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI) decreased significantly from baseline to 12 months, indicating an improvement in LV function and a reduction in LV size. In a high-volume tertiary center with extensive experience in advanced heart failure therapies and a dedicated ECMO team, ECMO-assisted PCI demonstrated feasibility and safety in patients with ischemic cardiomyopathy. However, the rate of complete revascularization was modest at 58%. Despite the high-risk profile of the patients, ECMO-assisted PCI was associated with a significant improvement in LV functional remodeling and a favorable 12-month survival rate. Further prospective studies are needed to confirm these findings and to identify the optimal patient and device selection criteria for ECMO-assisted PCI.

Hypertrophic Cardiomyopathy: From Medical Treatment to Advanced Heart Failure Therapies.

There has been much debate surrounding novel medical therapies and heart transplantation listing challenges in patients with hypertrophic cardiomyopathy (HCM). Recent clinical trials led to FDA approval of mavacamten (a cardiac myosin inhibitor), offering symptom relief and potentially delaying/avoiding invasive septal reduction therapies for some patients with HCM and left ventricular outflow obstruction (LVOTO). For those with refractory symptoms and end-stage heart failure, heart transplantation remains the gold standard. However, the concern for the organ allocation system failing to prioritize those individuals persists. HCM is a heterogeneous genetic condition with variable penetration and clinical presentation. Even though a large portion of patients remain asymptomatic, an important minority develops debilitating symptoms refractory to medical therapy. Post-HT short- and long-term outcomes are favorable. However, HT waitlist mortality remains high. For highly selected patients with HCM, a left ventricular assist device is a viable option.

Heart Failure Mortality in Chronic Kidney Disease: The Fatal Crossover

Real-world mortality data regarding heart failure in patients with comorbid chronic kidney disease remains limited, especially following the advent of advanced heart failure therapies. Using the CDC WONDER database, we included patients ≥ 25 years old who died primarily from heart failure (2011-2020) with comorbid chronic kidney disease. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals. We determined the trends over time by estimating the annual percent change (APC) using the Joinpoint regression program. There were 82,454 heart failure deaths with comorbid chronic kidney disease. The AAMR increased from 2.34 (95% CI, 2.28- 2.41) in 2011 to 4.79 (95% CI, 4.71- 4.88) in 2020. During the study period, Heart failure deaths among patients with comorbid chronic kidney disease increased by 149.0% compared to 59.9% in those without. Men had higher AAMR than women (3.92 [95% CI, 3.88- 3.96] vs. 2.96 [95% CI, 2.93- 2.99]). African American patients had the highest AAMR (5.85 [95% CI, 5.75- 5.96]). The Midwest region had the highest AAMR (3.83 [95% CI, 3.78- 3.89]). The AAMR was higher in the rural areas than in the urban regions (3.77 [95% CI, 3.71- 3.83] vs. 3.23 [95% CI, 3.20- 3.25]). Most patients died in hospices or nursing homes (29,000, 35.2%). Our study showed a significant increase in heart failure AAMR in patients with comorbid chronic kidney disease in recent eras. Further effort is needed to optimize cardioprotective agents for this population and to address demographic discrepancies at the policy level.

Denial for Advanced Heart Failure Therapies Due to Psychosocial Stressors: Who Comes Back?

BackgroundPsychosocial evaluations to assess candidacy for advanced heart failure therapies are not standardized across institutions, potentially contributing to disparities in approval for advanced therapies. Remediation rates of psychosocial stressors among patients with advanced HF and reconsideration for advanced therapies have not been well described. Methods and ResultsWe performed a retrospective, single-center study of 647 adults evaluated for heart transplant and VAD between 2014 and 2020, of whom 89 (14%) were denied for psychosocial stressors including caregiver, substance use, housing, financial, or mental health concerns. Later reevaluation occurred in 32 (36%) patients, of whom 23 were then approved. Patients initially declined were mostly male (76%), white (74%), and urban (79%). Reevaluation occurred in more women than men (43% vs 34%), black patients than white (43% vs 37%), and urban patients than rural (39% vs 28%). Patients had fewer psychosocial stressors at reevaluation (median=0.5) than at initial denial (median=2). Caregiver and substance use concerns were the most prevalent stressors in patients never returning for or subsequently denied at reevaluation. ConclusionsCaregiver and substance use concerns were common in patients denied for psychosocial reasons. Future efforts should focus on early screening for these stressors and implementation of a systematic reevaluation process.

Clinical Characteristics and Outcomes of Patients Suffering Acute Decompensated Heart Failure Complicated by Cardiogenic Shock.

Cardiogenic shock (CS) can stem from multiple causes and portends poor prognosis. Prior studies have focused on acute myocardial infarction-CS; however, acute decompensated heart failure (ADHF)-CS accounts for most cases. We studied patients suffering ADHF-CS to identify clinical factors, early in their trajectory, associated with a higher probability of successful outcomes. Consecutive patients with CS were evaluated (N=1162). We studied patients who developed ADHF-CS at our hospital (N=562). Primary end point was native heart survival (NHS), defined as survival to discharge without receiving advanced HF therapies. Secondary end points were adverse events, survival, major cardiac interventions, and hospital readmissions within 1 year following index hospitalization discharge. Association of clinical data with NHS was analyzed using logistic regression. Overall, 357 (63.5%) patients achieved NHS, 165 (29.2%) died, and 41 (7.3%) were discharged post advanced HF therapies. Of 398 discharged patients (70.8%), 303 (53.9%) were alive at 1 year. Patients with NHS less commonly suffered cardiac arrest, underwent intubation or pulmonary artery catheter placement, or received temporary mechanical circulatory support, had better hemodynamic and echocardiographic profiles, and had a lower vasoactive-inotropic score at shock onset. Bleeding, hemorrhagic stroke, hemolysis in patients with mechanical circulatory support, and acute kidney injury requiring renal replacement therapy were less common compared with patients who died or received advanced HF therapies. After multivariable adjustments, clinical variables associated with NHS likelihood included younger age, history of systemic hypertension, absence of cardiac arrest or acute kidney injury requiring renal replacement therapy, lower pulmonary capillary wedge pressure and vasoactive-inotropic score, and higher tricuspid annular plane systolic excursion at shock onset (all P<0.05). By studying contemporary patients with ADHF-CS, we identified clinical factors that can inform clinical management and provide future research targets. Right ventricular function, renal function, pulmonary artery catheter placement, and type and timing of temporary mechanical circulatory support warrant further investigation to improve outcomes of this devastating condition.

Concurrent Care and Use of Advanced Cardiac Therapies for Hospitalized Veterans With Heart Failure

ContextConcurrent care allows patients to receive hospice while continuing disease-directed therapies. This treatment model is available in the Veterans Administration (VA) medical system, but its use in Veterans with heart failure (HF) is unexplored. ObjectiveTo compare use of advanced HF therapies 30 days posthospitalization in Veterans on hospice versus not on hospice following admission for HF exacerbation. MethodsWe evaluated Veterans admitted for HF exacerbation to VA hospitals between Jan 2011 and June 2019 who received advanced HF therapies, hospice services, or both postdischarge. Concurrent care was defined as receiving both hospice services and advanced HF therapies. Demographics, comorbidities, and prior healthcare utilization were compared. Secondary outcomes included burdensome transitions and mortality. ResultsAmong 317,967 HF Veterans, 18,350 (5.8%) chose hospice posthospitalization. Only 58 hospice-enrolled Veterans (0.3%) received advanced HF therapies (i.e. concurrent care) within 30 days postdischarge. Of 299,617 Veterans not on hospice, 6,083 (2.0%) received advanced HF therapies (0.3% vs. 2.0%; P < 0.001). Veterans receiving concurrent care had higher six-month mortality than those receiving advanced HF therapies alone (77.6% vs. 14.9%, SMD 1.61). Hazard of burdensome transitions was similar (adjusted HR 1.44, 95% CI 0.95–2.17). ConclusionVeterans with HF receiving concurrent care were few and experienced higher mortality. Rate of burdensome transitions was similar between Veterans receiving concurrent care and those not on hospice. Further research may explore why Veterans infrequently utilize concurrent care at the end of life.

Prolonged Inotrope Use After Surgery for Congenital Heart Disease: A Common Occurrence with a High Burden of Mortality.

Outcomes in patients requiring prolonged inotropes (PI) following surgery for congenital heart disease (CHD) have not been well studied. We aimed to describe the burden of PI use in the immediate postoperative period after CHD surgery and identify risk factors for in-hospital mortality. We conducted a retrospective cohort study using the Pediatric Health Information System® (PHIS) database. Patients 0-18years with CHD who underwent cardiovascular surgery from 2010 to 2020 were included. Patients who received inotropic medications for > 7 consecutive days after surgery were in the PI group and all others in the control group. Patients who died before 7days were excluded. Multivariable mixed-effect logistic regression was used to examine risk factors for in-hospital mortality. There were 110,271 patients from 48 centers included, 10,292 in the PI group and 99,979 in the control group. In-hospital mortality was significantly higher in the PI group (24.9% vs. 4.6%, p < 0.001). Ventricular assist device use was rare (1.6%). After adjustment, odds of in-hospital mortality in the PI group was 3.5 (95% CI 3.3-3.8) times higher than in controls. Independent risk factors for in-hospital mortality were age, non-White race, class of CHD, number of complex chronic conditions, preoperative inotrope, preoperative extracorporeal membrane oxygenation, sepsis, stroke, renal failure, number of inotropes at 7days, and discharge year (p < 0.01 for all). Postoperative PI use in CHD is common and carries a considerable burden of mortality. Additional work is needed to understand which risk factors are modifiable and which patients may benefit from reintervention or advanced heart failure therapies.

Is Conduction System Pacing Going to Be the New Gold Standard for Cardiac Resynchronization Therapy?

The current gold standard in device therapy for advanced heart failure (HF), which has been firmly established in HF management for more than 25 years, is classical biventricular pacing (BiV-CRT). In the last decade, a new pacing modality called conduction system pacing (CSP) has emerged as a variant for advanced cardiac device therapy. It provides pacing with preserved intrinsic cardiac activation by direct stimulation of the specific cardiac conduction system. The term CSP integrates the modalities of HIS bundle pacing (HBP) and left bundle branch area pacing (LBBAP), both of which have provided convincing data in smaller randomized and big non-randomized studies for the prevention of pacemaker-induced cardiomyopathy and for providing effective cardiac resynchronization therapy in patients with classical CRT-indication (primary approach or after failed CRT). Recent American guidelines proposed the term "cardiac physiological pacing" (CPP), which summarizes CSP including left ventricular septal pacing (LVSP), a technical variant of LBBAP together with classical BiV-CRT. The terms HOT-CRT (HIS-optimized CRT) and LOT-CRT (LBBP-optimized CRT) describe hybrid technologies that combine CSP with an additional coronary-sinus electrode, which is sometimes useful in patients with advanced HF and diffuse interventricular conduction delay. If CSP continues providing promising data that can be confirmed in big, randomized trials, it is likely to become the new gold standard for patients with an expected high percentage of pacing (>20%), possibly also for cardiac resynchronization therapy. CSP is a sophisticated new treatment option that has the potential to raise the term "cardiac resynchronization therapy" to a new level. The aim of this review is to provide basic technical, anatomical, and functional knowledge of these new pacemaker techniques in order to facilitate the understanding of the different modalities, as well as to provide an up-to-date overview of the existing randomized and non-randomized evidence, particularly in direct comparison to right ventricular and classical biventricular pacing.

Treatment time limit for successful weaning from veno-arterial extracorporeal membrane oxygenation in cardiogenic shock.

Knowing the upper time limit for successful weaning from temporary mechanical circulatory support in cardiogenic shock will help with decision-making regarding advanced heart failure (HF) therapy or considering withdrawal of care. The aim of this study was to investigate the association between the support duration and successful weaning from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiogenic shock. A retrospective single-centre cohort study was conducted between January 2013 and June 2023. It included 100 consecutive patients with cardiogenic shock who were treated with VA-ECMO. Patients with out-of-hospital cardiac arrest were excluded. The primary outcome was successful weaning from VA-ECMO (i.e., VA-ECMO decannulation and survival to discharge). The association between the length of support duration and the weaning success rate was analysed. Patients were divided into three groups according to ECMO support duration: Group A (≤7days), Group B (8-14days), and Group C (≥15days). Multivariable logistic regression analysis was used to evaluate the impact of the length of support duration on successful weaning of VA-ECMO. The median age was 67years, and 73% of study participants were male. The underlying aetiologies of cardiogenic shock were as follows: acute myocardial infarction, 50; fulminant myocarditis, 19; cardiomyopathy, 15; valvular heart disease, 8; and other, 8. Seventy-five patients (75%) were attempted to wean VA-ECMO, and 67 moved on to decannulation. In total, 43 (43%) patients were successfully weaned from VA-ECMO. The median length of ECMO support duration was 8 [3-15] days. Compared with those who underwent successful ECMO decannulation, those who did not had a significantly longer support duration of VA-ECMO (5 [3-9] days vs. 12 [3-22] days, P=0.004). The weaning success rate was significantly higher in patients with short support duration; 58% (29/50), 40% (10/25), 16% (4/25) in Groups A, B, and C, respectively (P=0.002). Overall, none of the patients supported for over 24days (0/11) were successfully weaned from VA-ECMO. On multivariable logistic regression analysis, the length of support duration was independently associated with successful weaning after adjusting for age, sex, underlying aetiology, and left ventricular ejection fraction (odds ratio, 0.813 [per 3days]; 95% confidence interval, 0.679-0.914; P=0.025). Long support duration of VA-ECMO was significantly associated with a low rate of successful weaning in patients with cardiogenic shock. Patients who require VA-ECMO for over 1week should start considering advanced HF therapy or withdrawal of care.