Pathophysiology of heart failure and frailty: a common inflammatory origin?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136680/1/acel12581_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136680/2/acel12581.pd

CRT-700.34 Short-Term Outcomes Among Aortic Valve Stenosis Patients Undergoing Impella-Supported High-Risk Percutaneous Coronary Intervention

Background: Among patients undergoing percutaneous coronary intervention (PCI), severe aortic stenosis (AS) is associated with an increased risk of adverse outcomes. Although the use of mechanical circulatory support with Impella has been shown to improve 90-day outcomes in patients undergoing high-risk PCI (HRPCI), there is little information about the safety of this approach in pts with severe AS. We, therefore, sought to evaluate the efficacy and safety outcomes of Impella-supported HRPCI among patients with varying severity of AS. Methods: We studied patients enrolled in PROTECT III—a multicenter study of patients undergoing Impella-supported HRPCI. Patients were classified according to the severity of AS: none/trivial, mild, moderate, and severe. The primary outcome was the rate of major adverse cardiac and cerebrovascular events (MACCE) at 90 days, defined as the composite of all-cause death, MI, stroke/ TIA, and revascularization. Secondary outcomes included in-hospital PCI-related complications, stroke/TIA, and vascular complications requiring surgery. Results: Of 596 patients with echocardiographic data, 490 had no/trivial AS, and 34, 27, and 45 had mild, moderate, or severe AS, respectively. Patients with AS were older, less likely to have diabetes, more likely to have left main disease, and had higher left ventricular ejection fractions (Table). Severely calcified lesions and the use of atherectomy were more frequent among patients with moderate or severe AS. There were no differences in rates of PCI-related complications, stroke/TIA, 30-day MACCE, or 90-day MACCE according to AS severity. Rates of transfusion were higher among patients with AS—regardless of severity. Conclusion: Among patients undergoing Impella-supported HRPCI, PCI-related complications and 90-day outcomes did not differ based on AS status or severity

CRT-700.05 Impella Utilization in High-Risk Percutaneous Coronary Intervention Mitigates the Risks of Procedural and Clinical Adverse Events Independent of Left Ventricular Ejection Fraction: The Protect III Study

Background: Left ventricular (LV) dysfunction is associated with an increased risk of adverse events in patients undergoing percutaneous coronary intervention (PCI). However, the impact of LV ejection fraction (LVEF) on the outcomes of Impella-supported high-risk PCI (HRPCI) is unknown. Methods: Patients enrolled in the prospective, multicenter, and observational PROTECT III study from March 2017 to March 2020 who underwent Impella-supported HRPCI at the operator’s discretion (non-cardiogenic shock). Patients were divided into three tertiles (T) based on baseline LVEF: T1 (the lowest), T2, and T3 (the highest). The primary outcome is the rate of 90-day major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeated revascularization as adjudicated by an independent CEC. Results: Of 1237 patients, 940 with available baseline LVEF were analyzed. T1 included 353 patients (mean LVEF 19.6±4.7), T2 included 274 patients (mean LVEF 32.2±3.5), and T3 included 313 patients (mean LVEF 52.6±9.2). Patients in the higher tertiles were older, more likely to be females, presented more with acute coronary syndrome, and had more frequent left main disease. Also, severely calcified lesions and atherectomy utilization were more frequent in the higher tertiles. The rates of 90-day MACCE were comparable across all tertiles. Furthermore, PCI-related complications and 1-year mortality were also comparable (Table). After multivariable adjustment, 90-day MACCE was not significantly different between the LVEF tertiles (p=0.32). Conclusion: In patients with HRPCI supported by Impella, the rates of in-hospital adverse events, PCI-related complications, 90-day MACCE, and 1-year mortality were comparable among the different LVEF tertiles

TCT CONNECT-184 Impact of Sex and Timing of Impella Support in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock

Background: Randomized controlled trials studying Impella (Abiomed, Danvers, Massachusetts) usage in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) are limited. Retrospective data from the catheter-based Ventricular Assist Device Registry has demonstrated that pre-percutaneous coronary intervention (PCI) implantation of the device in AMICS patients is associated with a significant mortality benefit (odds ratio [OR]: 0.49, p = 0.04). Whether this effect varies by sex remains understudied. Methods: In-hospital data was collected from all AMICS patients prospectively enrolled in the RECOVER III post market approval observational study of the Impella device from 2017 to 2019. Univariate logistic regression models were used to identify the effects of baseline and procedural characteristics on in-hospital mortality. Identified statistically significant predictors and sex were included in the final multivariate logistic regression model. Results: Data were available for 82 females (41 with pre-PCI Impella vs. 41 with post-PCI Impella) and 266 males (167 pre-PCI vs. 99 post-PCI). Females had a survival benefit with Impella implantation pre-PCI compared to post-PCI (59% vs. 34%, p = 0.03); males did not (56% vs. 50%, p = 0.40). Survival for patients on 0, 1 to 2, or \u3e2 inotropes pre-Impella was 71%, 43%, and 19% for females (p = 0.001) and 64%, 54%, and 31% for males (p = 0.004), respectively. The multivariate regression found that the following were significant independent predictors of in-hospital mortality: pre-PCI Impella implantation (OR: 0.516, p = 0.03), previously diagnosed renal insufficiency (OR: 2.482, p = 0.02), heart rate (OR: 1.013, p = 0.03), and systolic blood pressure (OR: 1.013, p = 0.03). However, sex was not an independent predictor (p = 0.59) and there was not a significant interaction between sex and pre-PCI Impella usage (p = 0.13). Conclusion: Early implantation of Impella provides a significant survival benefit, particularly to females. Sex discrepancies appear to be the result of differing baseline and hemodynamic characteristics at presentation. Taking these factors into consideration may help identify patients most likely to benefit from Impella support

Left Ventricular Remodeling After Anterior-STEMI PCI: Imaging Observations in the Door-to-Unload (DTU) Pilot Trial

OBJECTIVES: To determine the predictive value of cardiac magnetic resonance (CMR) and echocardiographic parameters on left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) patients without cardiogenic shock and treated with mechanical LV unloading followed by immediate or delayed percutaneous coronary intervention (PCI)-mediated reperfusion. BACKGROUND: In STEMI, infarct size (IS) directly correlates with major cardiovascular outcomes. Preclinical models demonstrate mechanical LV unloading before reperfusion reduces IS. The door-to-unload (DTU)-STEMI pilot trial evaluated the safety and feasibility of LV unloading and delayed reperfusion in patients with STEMI. METHODS: This multicenter, prospective, randomized, safety and feasibility trial evaluated patients with anterior STEMI randomized 1:1 to LV unloading with the Impella CP (Abiomed) followed by immediate reperfusion vs delayed reperfusion after 30 minutes of unloading. Patients were assessed by CMR at 3-5 days and 30 days post PCI. Echocardiographic evaluations were performed at 3-5 and 90 days post PCI. At 3-5 days post PCI, patients were compared based on IS as percentage of LV mass (group 1 ≤25%, group 2 \u3e25%). Selection of IS threshold was performed post hoc. RESULTS: Fifty patients were enrolled from April 2017 to May 2018. At 90 days, group 1 (IS ≤25%) exhibited improved LV ejection fraction (from 53.1% to 58.9%; P=.001) and group 2 (IS \u3e25%) demonstrated no improvement (from 37.6% to 39.1%; P=.55). LV end-diastolic volume and end-systolic volume were unchanged in group 1 and worsened in group 2. There was correlation between 3-5 day and 30-day CMR measurements of IS and 90-day echocardiography-derived LV ejection fraction. CONCLUSIONS: Immediate 3-5 day post-therapy IS by CMR correlates with 90-day echocardiographic LVEF and indices of remodeling. Patients with post-therapy IS \u3e25% demonstrated evidence of adverse remodeling. Larger studies are needed to corroborate these findings with implications on patient management and prognosis

Renal tubular resistance is the primary driver for loop diuretic resistance in acute heart failure

Background: Loop diuretic resistance is a common barrier to effective decongestion in acute heart failure (AHF), and is associated with poor outcome. Specific mechanisms underlying diuretic resistance are currently unknown in contemporary AHF patients. We therefore aimed to determine the relative importance of defects in diuretic delivery vs. renal tubular response in determining diuretic response (DR) in AHF. Methods and results: Fifty AHF patients treated with intravenous bumetanide underwent a 6-h timed urine collection for sodium and bumetanide clearance. Whole-kidney DR was defined as sodium excreted per doubling of administered loop diuretic and represents the sum of defects in drug delivery and renal tubular response. Tubular DR, defined as sodium excreted per doubling of renally cleared (urinary) loop diuretic, captures resistance specifically in the renal tubule. Median administered bumetanide dose was 3.0 (2.0-4.0) mg with 52 (33-77)% of the drug excreted into the urine. Significant between-patient variability was present as the administered dose only explained 39% of variability in the quantity of bumetanide in urine. Cumulatively, factors related to drug delivery such as renal bumetanide clearance, administered dose, and urea clearance explained 28% of the variance in whole-kidney DR. However, resistance at the level of the renal tubule (tubular DR) explained 71% of the variability in whole-kidney DR. Conclusion: Defects at the level of the renal tubule are substantially more important than reduced diuretic delivery in determining diuretic resistance in patients with AHF

Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement

Frailty is increasingly recognized as a salient condition in patients with heart failure (HF) as previous studies have determined that frailty is highly prevalent and prognostically significant, particularly in those with advanced HF. Definitions of frailty have included a variety of domains, including physical performance, sarcopenia, disability, comorbidity, and cognitive and psychological impairments, many of which are common in advanced HF. Multiple groups have recently recommended incorporating frailty assessments into clinical practice and research studies, indicating the need to standardize the definition and measurement of frailty in advanced HF. Therefore, the purpose of this consensus statement is to provide an integrated perspective on the definition of frailty in advanced HF and to generate a consensus on how to assess and manage frailty. We convened a group of HF clinicians and researchers who have expertise in frailty and related geriatric conditions in HF, and we focused on the patient with advanced HF. Herein, we provide an overview of frailty and how it has been applied in advanced HF (including potential mechanisms), present a definition of frailty, generate suggested assessments of frailty, provide guidance to differentiate frailty and related terms, and describe the assessment and management in advanced HF, including with surgical and nonsurgical interventions. We conclude by outlining critical evidence gaps, areas for future research, and clinical implementation

Hypochloremia and Diuretic Resistance in Heart Failure: Mechanistic Insights

Background-Recent epidemiological studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure. Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiological literature. Methods and Results-Two heart failure cohorts were included: (1) observational: patients receiving loop diuretics at the Yale Transitional Care Center (N=162) and (2) interventional pilot: stable outpatients receiving >= 80 mg furosemide equivalents were studied before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10). At the Yale Transitional Care Center, 31.5% of patients had hypochloremia (chloride Conclusions-Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation was associated with increases in serum chloride and changes in several cardiorenal parameters