Protocol-driven approach to guideline-directed medical therapy optimization for heart failure: A real-world application to recovery.

The objective of our study was to evaluate the real-world effects of an aggressive, personalized protocol for guideline-directed medical therapy (GDMT) titration in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We conducted a two-center retrospective cohort study. Patients with HFrEF who presented to a HF clinic from January 2020 to December 2022 were placed on a GDMT protocol. 180 patients were included in the study. Mean GDMT score significantly increased from 4.7 to 5.9 (p < 0.001) between initial and final visits. Mean left ventricular ejection fraction (LVEF) significantly increased from 28 % to 33 % (+5 %, p < 0.001). 27 (15.7 %) of the 172 patients with complete New York Heart Association (NYHA) classification data had improvement by at least 1 class, while 2 (1.2 %) patients had worsening NYHA classification. 140 (77.8 %) patients had no unplanned hospitalizations between visits. 21 (11.7 %) patients had an unplanned hospitalization for acute HF during the study period with a mean time from first clinic visit to hospitalization of 183 days (range: 13-821 days). 2 (1.1 %) patients were hospitalized due to GDMT-associated adverse drug events (i.e. hypotension, hyperkalemia). 7 (3.9 %) patients died during the study period, which was lower than the predicted 1-year death rate for our cohort (12.3 %) using the MAGGIC score. In conclusion, an aggressive, personalized protocol for GDMT titration in patients with HFrEF led to significant improvements in LVEF, NYHA classification, hospitalization, and mortality in a real-world setting. This protocol may help serve as a road map to lessen the gap between clinical knowledge and practice surrounding optimization of GDMT and move HFrEF patients toward a path to recovery.

Transthyretin cardiac amyloid: Broad heart failure phenotypic spectrum and implications for diagnosis.

AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) is most often associated with heart failure with preserved ejection fraction (HFpEF). However, patients may present with impaired systolic function at the time of diagnosis, which has not been widely investigated. We sought to explore the prevalence of various heart failure (HF) phenotypes and their associated clinical characteristics at the time of ATTR-CA diagnosis. METHODS: We performed a single-centre retrospective cohort study of consecutive patients with ATTR-CA evaluated between February 2016 and December 2022. Data on patient demographics, comorbidities, imaging and laboratory findings were compared across HF phenotypes (age: 78.1 ± 8.6 years, with 91.1% male). A total of 21.6% (n = 46) presented with heart failure with reduced ejection fraction (HFrEF), 17.8% (n = 38) with heart failure with mildly reduced ejection fraction (HFmrEF) and 60.6% (n = 129) with HFpEF at the time of diagnosis with ATTR-CA. Those presenting with HFrEF or HFmrEF were more likely to be African American and had significantly worse New York Heart Association (NYHA) functional class, higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and higher serum creatinine levels as compared with those with HFpEF. CONCLUSIONS: Although ATTR-CA is traditionally thought to be seen primarily among patients with HFpEF, our data suggest that ATTR-CA has a higher prevalence among patients with HFrEF, which underscores the importance of heightened clinical suspicion regardless of ejection fraction when considering ATTR-CA. Furthermore, although comorbidities are similar, patients with HFmrEF and HFrEF had a worse symptom burden.

Guide to Temporary Mechanical Support in Cardiogenic Shock: Choosing Wisely.

Cardiogenic shock is a multisystem pathology that carries a high mortality rate, and initial pharmacotherapies include the use of vasopressors and inotropes. These agents can increase myocardial oxygen consumption and decrease tissue perfusion that can oftentimes result in a state of refractory cardiogenic shock for which temporary mechanical circulatory support can be considered. Numerous support devices are available, each with its own hemodynamic blueprint. Defining a patient's hemodynamic profile and understanding the phenotype of cardiogenic shock is important in device selection. Careful patient selection incorporating a multidisciplinary team approach should be utilized.

PREDICT HF: Risk stratification in advanced heart failure using novel hemodynamic parameters.

BACKGROUND: Invasive hemodynamics are fundamental in assessing patients with advanced heart failure (HF). Several novel hemodynamic parameters have been studied; however, the relative prognostic potential remains ill-defined. HYPOTHESIS: Advanced hemodynamic parameters provide additional prognostication beyond the standard hemodynamic assessment. METHODS: Patients from the PRognostic Evaluation During Invasive CaTheterization for Heart Failure (PREDICT-HF) registry who underwent right heart catheterization (RHC) were included in the analysis. The primary endpoint was survival to orthotopic heart transplant (OHT) or durable left ventricular assist device (LVAD), or death within 6 months of RHC. RESULTS: Of 846 patients included, 176 (21%) met the primary endpoint. In a multivariate model that included traditional hemodynamic variables, pulmonary capillary wedge pressure (PCWP) (OR: 1.10, 1.04-1.15, p < .001), and cardiac index (CI) (OR: 0.86, 0.81-0.92, p < .001) were shown to be predictive of adverse outcomes. In a separate multivariate model that incorporated advanced hemodynamic parameters, cardiac power output (CPO) (OR: 0.76, 0.71-0.83, p < .001), aortic pulsatility index (API) (OR: 0.94, 0.91-0.96, p < .001), and pulmonary artery pulsatility index (OR: 1.02, 1.00-1.03, p .027) were all significantly associated with the primary outcome. Positively concordant API and CPO afforded the best freedom from the endpoint (94.7%), whilst negatively concordant API and CPO had the worst freedom from the endpoint (61.5%, p < .001). Those with discordant API and CPO had similar freedom from the endpoint. CONCLUSION: The advanced hemodynamic parameters API and CPO are independently associated with death or the need for OHT or LVAD within 6 months. Further prospective studies are needed to validate these parameters and elucidate their role in patients with advanced HF.

Predictors of developing renal dysfunction following diagnosis of transthyretin cardiac amyloidosis.

BACKGROUND: In patients with transthyretin cardiac amyloidosis (ATTR-CA), renal dysfunction is a poor prognostic indicator. Limited data are available on variables that portend worsening renal function (wRF) among ATTR-CA patients. OBJECTIVES: This study assesses which characteristics place patients at higher risk for the development of wRF (defined as a drop of ≥10% in glomerular filtration rate [GFR]) within the first year following diagnosis of ATTR-CA. METHODS: We included patients with ATTR-CA (n = 134) evaluated between 2/2016 and 12/2022 and followed for up to 1 year at our amyloid clinic. Patients were stratified into two groups: a group with maintained renal function (mRF) and a group with wRF and compared using appropriate testing. Significant variables in the univariate analysis were included in the multivariable logistic regression model to determine characteristics associated with wRF. RESULTS: Within a follow-up period of 326 ± 118 days, the median GFR% change measured -6% [-18%, +8]. About 41.8% (n = 56) had wRF, while the remainder had mRF. In addition, in patients with no prior history of chronic kidney disease (CKD), 25.5% developed de novo CKD. On multivariable logistic regression, only New York Heart Association (NYHA) class ≥III (odds ratio [OR]: 3.9, 95% confidence interval [CI]: [1.6-9.3]), history of ischemic heart disease (IHD) (OR: 0.3, 95% CI: [0.1-0.7]), and not receiving SGLT-2i (OR: 0.1, 95% CI: [0.02-0.5]) were significant predictors of wRF. CONCLUSION: Our study demonstrated that the development of de novo renal dysfunction or wRF is common following the diagnosis of ATTR-CA. Additionally, we identified worse NYHA class and no prior history of IHD as significant predictors associated with developing wRF, while receiving SGLT-2i therapy appeared to be protective in this population.

A review of the contemporary use of inotropes in patients with heart failure.

PURPOSE OF REVIEW: The role of inotropes has evolved with its use now expanding over multiple indications including cardiogenic shock, low cardiac output states, bridging therapy to transplant or mechanical support, and palliative care. There remains no consensus as to the recommended inotrope for the failing heart. We aim to provide an overview of the recent literature related to inotrope therapy and its application in patients with advanced heart failure and hemodynamic compromise. RECENT FINDINGS: In this review, we outline various clinical scenarios that warrant the use of inotrope therapy and the associated recommendations. There remains no mortality benefit with inotrope use. Per American Heart Association recommendations, the choice of the inotropic agent should be guided by parameters such as blood pressure, concurrent arrhythmias, and availability of the medication. Outcome variability remains a heightened concern with inpatient inotropic use in both hemodynamically stable and unstable patients. Finally, inotropic use in palliative care continues to be a recommendation for symptom control and improvement in functional status when the appropriate social support is present for the patient. SUMMARY: In summary, the ideal inotropic agent remains at the discretion of the clinical provider. Different clinical scenarios may favor one agent over another based on the type of cardiogenic shock and mechanism of action of the inotrope. A future shift towards characterizing inotrope use based on subgroup cardiogenic shock profiles may be seen, however further studies are needed to better understand these phenotypes. Inotrope therapy remains a keystone to bridging to advanced therapies and palliative care.

Guide to Temporary Mechanical Support in Cardiogenic Shock: Choosing Wisely.

Cardiogenic shock is a multisystem pathology that carries a high mortality rate, and initial pharmacotherapies include the use of vasopressors and inotropes. These agents can increase myocardial oxygen consumption and decrease tissue perfusion that can oftentimes result in a state of refractory cardiogenic shock for which temporary mechanical circulatory support can be considered. Numerous support devices are available, each with its own hemodynamic blueprint. Defining a patient's hemodynamic profile and understanding the phenotype of cardiogenic shock is important in device selection. Careful patient selection incorporating a multidisciplinary team approach should be utilized.

Variation in Hemodynamic Assessment and Interpretation: A Call to Standardize the Right Heart Catheterization.

BACKGROUND: Invasive hemodynamic measurement via right heart catheterization has shown divergent data in its role in the treatment of patients with heart failure (HF) and cardiogenic shock. We hypothesized that variation in data acquisition technique and interpretation might contribute to these observations. We sought to assess differences in hemodynamic acquisition and interpretation by operator subspecialty as well as level of experience. METHODS AND RESULTS: Individual-level responses to how physicians both collect and interpret hemodynamic data at the time of right heart catheterization was solicited via a survey distributed to international professional societies in HF and interventional cardiology. Data were stratified both by operator subspecialty (HF specialists or interventional cardiologists [IC]) and operator experience (early career [≤10 years from training] or late career [>10 years from training]) to determine variations in clinical practice. For the sensitivity analysis, we also look at differences in each subgroup. A total of 261 responses were received. There were 141 clinicians (52%) who self-identified as HF specialists, 99 (38%) identified as IC, and 20 (8%) identified as other. There were 142 early career providers (54%) and late career providers (119 [46%]). When recording hemodynamic values, there was considerable variation in practice patterns, regardless of subspecialty or level of experience for the majority of the intracardiac variables. There was no agreement or mild agreement among HF and IC as to when to record right atrial pressures or pulmonary capillary wedge pressures. HF cardiologists were more likely to routinely measure both Fick and thermodilution cardiac output compared with IC (51% vs 29%, P < .001), something mirrored in early career vs later career cardiologists. CONCLUSIONS: Significant variation exists between the acquisition and interpretation of right heart catheterization measurements between HF and IC, as well as those early and late in their careers. With the growth of the heart team approach to management of patients in cardiogenic shock, standardization of both assessment and management practices is needed.

Trends and Outcomes of Left Atrial Appendage Occlusion in Renal and Liver Transplant Recipients: Insights From the United States National Inpatient and Readmission Database.

Left atrial appendage occlusion using the Watchman device has emerged as an alternative treatment strategy for preventing strokes in patients with atrial fibrillation. However, there is no data on its safety and clinical outcomes in prior renal or liver transplant recipients. We included a total of 61,995 patients from the National Inpatient Sample (NIS, in-hospital outcomes) and 55,048 patients from the National Readmission Database (NRD, 30-day outcomes) who underwent percutaneous left atrial appendage occlusion (LAAO). From this group, 0.65% (n=405) and 0.62% (n=339) were renal and liver transplant recipients in NIS and NRD respectively. Transplant recipients were younger compared with non-transplant recipients (mean age 69 vs 77 years, P=<0.01). There was little difference in terms of in-hospital mortality (0% vs 0.2%, P=0.43), major complications (6.2% vs 5.6%, P=0.61), cardiovascular complications (2.5% vs 2.8%, P=0.73), neurological complications (1.2% vs 0.7%, P=0.21) or bleeding complications (1.2% vs 0.7%, P=0.99) between transplant vs. non-transplant patients. Based on the NRD database, 30-day readmission rate was not meaningfully different for transplant recipients undergoing LAAO (9.44%) when compared to non-transplant patients (8.12%, [log-rank, P=0.56]). There was no difference between 30-day major or cardiovascular complications, however vascular complication rates were significantly higher for transplant recipients (OR 2.56, 95% CI [(1.66-3.47]). Our study findings suggest that LAAO may be safe for patients with a prior renal or liver transplant in terms of major complications, cardiovascular complications, and all-cause readmission rates. However vascular complications may be higher in transplant recipients. Further large-scale studies are needed to confirm these findings.

Favorable Hemocompatibility in HeartMate 3 May Prevent Thrombosis After Prolonged Pump Cessation.

The HeartMate 3 Left Ventricular Assist System has demonstrated a reduction in risk of pump thrombosis. The improved hemocompatibility of this device is largely attributed to the pump mechanics including a large-diameter outflow graft, increased retrograde flow through the pump during pump cessation, and the textured blood-contacting surfaces of the pump. We present a 55-year-old man with a HeartMate 3 device who presented with heart failure symptoms, prolonged pump cessation for 7 days, and subtherapeutic anticoagulation therapy. Despite prolonged pump cessation and interrupted anticoagulation therapy, there was no evidence of pump thrombosis as determined by both laboratory and imaging studies. This case suggests favorable hemocompatibility of the HeartMate 3 device, which clinicians may consider in the management of patients needing advanced therapies.

Use of Intracardiac Echocardiography to Evaluate Continuous-Flow Left Ventricular Assist Device Function in a Man With Obesity.

Aortic insufficiency with recirculation can be difficult to diagnose echocardiographically in patients who have continuous-flow left ventricular assist devices. Transthoracic and transesophageal echocardiography can underestimate its severity; moreover, transesophageal echocardiography necessitates general anesthesia. We report the case of a 58-year-old man with obesity and end-stage nonischemic cardiomyopathy who, after 3 months of support with a continuous-flow left ventricular assist device, underwent intracardiac echocardiography to evaluate complications potentially associated with the device. The findings ruled out aortic insufficiency, preventing an unnecessary valvular intervention.

Characteristics and Outcomes Based on Perceived Illness Severity in SARS-CoV-2.

OBJECTIVES: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) epidemic is characterized by a global sense of uncertainty, partly driven by the paucity of real-life clinical data. This study assessed whether admission patient characteristics were associated with need for intensive care unit (ICU) care. METHODS: The observational study included consecutive patients admitted to a large community teaching hospital with a diagnosis of SARS-CoV-2 between March 6, 2020 and March 31, 2020. Comparisons were made based on the need for ICU admission. RESULTS: A total of 156 patients were admitted, 42 of whom (26.9%) required ICU admission and 114 (73.1%) did not. No difference in age (61.9 years vs 60.5 years, P = 0.67), race/ethnicity, or comorbidities were noted, except that patients requiring ICU care had lower serum albumin levels and lymphocyte counts and higher liver function tests, white blood cell count, and absolute neutrophil count on admission. The average time from admission to death was similar (10 days in an ICU subset vs 9.2 days in a non-ICU subset, P = 0.78), yet patients necessitating ICU care had longer hospital lengths of stay (10.2 vs 5.1 days, P = 0.0002). At the time of data extraction, 15 patients in the ICU had died, 7 were discharged from the hospital, and 20 were still admitted while 5 patients died in the non-ICU cohort with 97 discharged and 12 patients admitted. CONCLUSIONS: This is the largest study assessing clinical differences based on the need for ICU admission in inpatients with SARS-CoV-2. It found few major differences in clinical variables between subsets. Among patients admitted to the ICU, outcomes were generally poor.

Expected vs Actual Outcomes of Elective Initiation of Inotropic Therapy During Heart Failure Hospitalization.

OBJECTIVE: To describe the intent and early outcomes of elective inotrope use during heart failure hospitalization. PATIENTS AND METHODS: A prospective multisite design was used to collect data for hemodynamically stable patients started electively on inotrope therapy between January 1 and August 31, 2018. We prospectively recorded data when intravenous inotropic therapy was initiated, including survey of the attending cardiologists regarding expectations for the clinical course. Patients were followed up for events through hospital discharge and an additional survey was administered at the end of hospitalization. RESULTS: For the 92 patients enrolled, average age was 60 years and ejection fraction was 24%±12%. At the time of inotrope initiation, attending heart failure cardiologists predicted that 50% (n=46) of the patients had a "high or very high" likelihood of becoming dependent on intravenous inotropic therapy and 58% (n=53) had a "high" likelihood of death, transplant, or durable ventricular assist device placement within the next 6 months. Provider predictions regarding death/hospice or need for continued home infusions were accurate only 51% (47 of 92) of the time. Only half the patients (n=47) had goals-of-care conversations before inotrope treatment initiation. CONCLUSION: More than half the patients (51 of 92) electively started on inotrope treatment without present or imminent cardiogenic shock ultimately required home inotrope therapy, died during admission, or were discharged with hospice. Heart failure clinicians could not reliably identify those patients at the time of inotrope therapy initiation and goals-of-care discussions were not frequently performed.

Canine-Assisted Therapy in Hospitalized Patients Awaiting Heart Transplantation.

OBJECTIVES: Patients awaiting heart transplantation can be listed for prolonged periods of time and, as a result, the prevalence of anxiety and depression is high. Our study evaluates the feasibility of canine-assisted therapy (CAT) in this population. METHODS: A prospective, multicenter study was performed on all status 1a patients admitted during a 12-month period to await transplantation. Patients were asked to complete the Generalized Anxiety Disorder 7-item scale and the Patient Health Questionnaire-9 at baseline, week 2, and week 6, and the Perceived Stress Scale at baseline and week 4. At the conclusion of the study, patients completed a questionnaire assessing the overall efficacy of CAT. RESULTS: Baseline measures demonstrated high levels of anxiety, depression, and stress. The complete Generalized Anxiety Disorder 7-item scale (average score 10.9 vs 8; P = 0.14) and the Patient Health Questionnaire-9 (average score 12.3 vs 9.5; P = 0.057) scores decreased from baseline to week 6 and the Perceived Stress Scale (average score 29.8 vs 27; P = 0.16) decreased from baseline to week 4 with trends toward significance. All of the patients perceived CAT as improving the overall quality of hospitalization, would recommend CAT to other patients, and would elect for CAT during subsequent admissions. No infectious concerns were reported. CONCLUSIONS: Anxiety, stress, and depression are prevalent among 1a heart transplantation candidates, and CAT is a welcomed adjunct to the usual medical care in this population.

The Many Faces of Heart Failure.

Heart failure is a heterogeneous clinical syndrome stemming from cardiac overload and injury that leads to considerable morbidity and mortality. This review highlights the many faces of heart failure, a major and growing public health problem, including its causes, classification, underlying pathophysiology, and variable progression. An individualized, patient-centered treatment approach that focuses on guideline-directed pharmacologic and device therapies is required for optimal management of this complex syndrome.

Low to Intermediate Dose Atropine Administration During Dobutamine Stress Echocardiography in the Pre-Liver Transplant Population.

INTRODUCTION: Dobutamine stress echocardiography (DSE) is frequently used to screen for obstructive coronary artery disease in the pre-liver transplant evaluation. Although atropine is a commonly used adjunctive medication, no study has evaluated its side effect profile in patients with end-stage liver disease (ESLD). RESEARCH QUESTION: What is the safety of atropine in candidates undergoing pre-liver transplant evaluation when atropine is used in stress testing? DESIGN: This multicenter, prospective study enrolled patients over a 6-month period undergoing pre-liver transplant evaluation. Each patient completed a questionnaire assessing anticholinergic-related symptoms within 24 hours of testing and 48 hours following. Comparisons were made among patients receiving any atropine dose versus those who did not and among patients receiving at least 1 mg atropine and those receiving less/none. RESULTS: Forty patients were evaluated, and 32 (80%) had adjunctive atropine administered. No differences in clinical characteristics were noted. In comparisons among patients receiving any dose of atropine with those who did not, questionnaire results indicated a higher rate of nausea prior to testing and higher overall symptom severity following testing in patients not receiving atropine. In comparisons among patients receiving less than 1 mg atropine with those receiving at least 1 mg atropine, no difference in pre- or posttesting questionnaire responses was present. No patient in the study required reversal agents or hospitalization within 7 days of testing. CONCLUSIONS: Atropine, a hepatically metabolized medication, did not predispose patients with ESLD to an increased symptom burden, and clinical outcomes related to DSE were unaffected.

Genomewide association study reveals novel genetic loci associated with change in renal function in heart transplant recipients.

BACKGROUND: Renal dysfunction occurs commonly after heart transplantation (HTx) with wide inter-individual variability but whether a genetic predisposition exists in these patients is unknown. Genomewide association studies (GWAS) have not been performed to assess the association of genetic variation with change in renal function after HTx. METHODS: Clinical and demographic data of patients who underwent HTx and provided blood samples and consent for genetic analysis were included. Genotyping was performed using Illumina Infinium Human CoreExome v1.0 analysis kit. A GWAS utilizing linear regression models was performed with estimated glomerular filtration rate (eGFR) at 1 year as the phenotype after adjusting for baseline eGFR prior to HTx and conversion from calcineurin inhibitor to sirolimus as primary immunosuppression therapy. RESULTS: A total of 251 HTx recipients were genotyped for 314,903 single nucleotide polymorphisms (SNPs). The mean (SD) age was 50 (12.5) years; most patients were of European origin (n = 243, 96.8%) and males (n = 179, 71.3%). After adjustment for potential confounders, two variants, rs17033285 (P = 4.3 × 10-7 ) and rs4917601 (P = 6.46 × 10-7 ), in a long non-coding RNA (lncRNA) gene LINC01121 and a pseudogene BTBD7P2, were identified to have a significant association with change in GFR at 1 year after HTx. CONCLUSIONS: Our first of its kind GWAS demonstrates that genetic variation affects renal function after HTx independent of other risk factors. Agnostic genetic approaches such as these may lead to identification of novel biological pathways such as the role of lncRNAs in the development of renal dysfunction post-HTx.

Serum albumin concentration as an independent prognostic indicator in patients with pulmonary arterial hypertension.

BACKGROUND: Serum albumin is a strong prognostic indicator for many disease processes, yet limited data exist regarding its prognostic relationship in pulmonary arterial hypertension (PAH). Our study aims to assess the relationship of hypoalbuminemia with disease severity and mortality in this population. HYPOTHESIS: Serum albumin concentrations are a predictor of outcomes in PAH. METHODS: A retrospective review of all patients with World Health Organization group 1 PAH evaluated between March 2001 and August 2008 was performed. Patients were stratified into groups based on serum albumin concentration ≤3.3 g/dL (hypoalbuminemia) vs >3.3 g/dL. Clinical, hemodynamic, and survival comparisons were compared between groups using Student t test and χ2 test, followed by univariate analysis and multivariate logistic regression. RESULTS: A total of 163/273 (59.7%) patients had a documented serum albumin concentration. Hypoalbuminemia was present in 41 (25.2%) patients and serum albumin ≤3.3 g/dL represented the lowest quartile of serum albumin. Patients with hypoalbuminemia had higher rates of renal dysfunction (26.8% vs 9.8%, P =0.0069) and hepatic dysfunction (29.3% vs 6.6%, P <0.001), and lower hemoglobin levels (11.6 vs 13.4 g/dL, P < 0.001). Hemodynamic and functional capacity assessments were comparable between groups. Independent predictors of mortality included low albumin levels (hazard ratio [HR]: 0.485, P = 0.008), high right atrial systolic area (HR: 1.062, P = 0.003), low Fick-derived cardiac index (HR: 1.465, P = 0.016), and high New York Heart Association functional class (HR: 1.767, P = 0.042). Patients with hypoalbuminemia demonstrated a significantly lower survival rate at latest follow-up (P = 0.01). CONCLUSIONS: Lower serum albumin concentrations in patients with PAH are associated with higher mortality and can serve as a marker of disease severity in this patient population.