Artificial Intelligence-Derived Electrocardiogram Assessment of Cardiac Age and Molecular Markers of Senescence in Heart Failure.

OBJECTIVE: To ascertain whether heart failure (HF) itself is a senescent phenomenon independent of age, and how this is reflected at a molecular level in the circulating progenitor cell niche, and at a substrate level using a novel electrocardiogram (ECG)-based artificial intelligence platform. PATIENTS AND METHODS: Between October 14, 2016, and October 29, 2020, CD34+ progenitor cells were analyzed by flow cytometry and isolated by magnetic-activated cell sorting from patients of similar age with New York Heart Association functional classes IV (n = 17) and I-II (n = 10) heart failure with reduced ejection fraction and healthy controls (n = 10). CD34+ cellular senescence was quantitated by human telomerase reverse transcriptase expression and telomerase expression by quantitative polymerase chain reaction, and senescence-associated secretory phenotype (SASP) protein expression assayed in plasma. An ECG-based artificial intelligence (AI) algorithm was used to determine cardiac age and difference from chronological age (AI ECG age gap). RESULTS: CD34+ counts and telomerase expression were significantly reduced and AI ECG age gap and SASP expression increased in all HF groups compared with healthy controls. Expression of SASP protein was closely associated with telomerase activity and severity of HF phenotype and inflammation. Telomerase activity was more closely associated with CD34+ cell counts and AI ECG age gap. CONCLUSION: We conclude from this pilot study that HF may promote a senescent phenotype independent of chronological age. We show for the first time that the AI ECG in HF shows a phenotype of cardiac aging beyond chronological age, and appears to be associated with cellular and molecular evidence of senescence.

Sequential organ failure assessment score improves survival prediction for left ventricular assist device recipients in intensive care.

BACKGROUND: Preoperative risk scores facilitate patient selection, but postoperative risk scores may offer valuable information for predicting outcomes. We hypothesized that the postoperative Sequential Organ Failure Assessment (SOFA) score would predict mortality after left ventricular assist device (LVAD) implantation. METHODS: We retrospectively reviewed data from 294 continuous-flow LVAD implantations performed at Mayo Clinic Rochester during 2007 to 2015. We calculated the EuroSCORE, HeartMate-II Risk Score, and RV Failure Risk Score from preoperative data and the APACHE III and Post Cardiac Surgery (POCAS) risk scores from postoperative data. Daily, maximum, and mean SOFA scores were calculated for the first 5 postoperative days. The area under receiver-operator characteristic curves (AUC) was calculated to compare the scoring systems' ability to predict 30-day, 90-day, and 1-year mortality. RESULTS: For the entire cohort, mortality was 5% at 30 days, 10% at 90 days, and 19% at 1 year. The Day 1 SOFA score had better discrimination for 30-day mortality (AUC 0.77) than the preoperative risk scores or the APACHE III and POCAS postoperative scores. The maximum SOFA score had the best discrimination for 30-day mortality (AUC 0.86), and the mean SOFA score had the best discrimination for 90-day mortality (AUC 0.82) and 1-year mortality (AUC 0.76). CONCLUSIONS: We observed that postoperative mean and maximum SOFA scores in LVAD recipients predict short-term and intermediate-term mortality better than preoperative risk scores do. However, because preoperative and postoperative risk scores each contribute unique information, they are best used in concert to predict outcomes after LVAD implantation.

Aortic Stenosis and Coronary Artery Disease: Cost of Transcatheter vs Surgical Management.

BACKGROUND: Surgical aortic valve replacement with coronary artery bypass grafting (SAVR+CABG) is the recommended treatment for aortic stenosis and coronary artery disease; however, percutaneous coronary intervention at the time of transcatheter aortic valve replacement (TAVR+PCI) is used with increasing frequency. METHODS: Using the National Inpatient Sample, we identified all adult admissions with a diagnosis of aortic stenosis. Subgroups of SAVR+CABG and TAVR+PCI formed the study group. Outcomes of interest included total hospitalization charges, temporal trends, in-hospital mortality, and complications. RESULTS: Between 2012 and 2017, a total of 97 955 admissions (95.9%) received SAVR+CABG, and 4240 (4.1%) received TAVR+PCI; the proportion of TAVR+PCI increased from 1% in 2012 to 9.2% in 2017 (P < .001). Compared with patients receiving TAVR+PCI, admissions receiving SAVR+CABG were younger, more likely to be male, and had lower comorbidity (all P < .001). Adjusted in-hospital mortality was comparable in both groups (odds ratio 0.94; 95% confidence interval, 0.79 to 1.11; P = .45). Higher rates of pacemaker implantation, cardiac arrest, and vascular complications were seen in the TAVR+PCI group, whereas SAVR+CABG was associated with a greater requirement for prolonged ventilation. Admissions receiving TAVR+PCI had shorter lengths of hospital stay and were more likely to be discharged home. Nevertheless, the TAVR+PCI group had higher hospitalization charges compared with the SAVR+CABG group (all P < .001). CONCLUSIONS: There has been a steady increase in the use of percutaneous strategies for aortic stenosis and coronary artery disease management. In-hospital mortality was comparable in SAVR+CABG and TAVR+PCI groups, but despite shorter in-hospital stays, TAVR+PCI was associated with higher cardiac and vascular complication rates and hospitalization charges.

Temporal Trends, Clinical Characteristics, and Outcomes of Emergent Coronary Artery Bypass Grafting for Acute Myocardial Infarction in the United States.

Background There are limited contemporary data on the use of emergent coronary artery bypass grafting (CABG) in acute myocardial infarction. Methods and Results Adult (aged >18 years) acute myocardial infarction admissions were identified using the National (Nationwide) Inpatient Sample (2000-2017) and classified by tertiles of admission year. Outcomes of interest included temporal trends of CABG use; age-, sex-, and race-stratified trends in CABG use; in-hospital mortality; hospitalization costs; and hospital length of stay. Of the 11 622 528 acute myocardial infarction admissions, emergent CABG was performed in 1 071 156 (9.2%). CABG utilization decreased overall (10.5% [2000] to 8.7% [2017]; adjusted odds ratio [OR], 0.98 [95% CI, 0.98-0.98]; P<0.001), in ST-segment-elevation myocardial infarction (10.2% [2000] to 5.2% [2017]; adjusted OR, 0.95 [95% CI, 0.95-0.95]; P<0.001) and non-ST-segment-elevation myocardial infarction (10.8% [2000] to 10.0% [2017]; adjusted OR, 0.99 [95% CI, 0.99-0.99]; P<0.001), with consistent age, sex, and race trends. In 2012 to 2017, compared with 2000 to 2005, admissions receiving emergent CABG were more likely to have non-ST-segment-elevation myocardial infarction (80.5% versus 56.1%), higher rates of noncardiac multiorgan failure (26.1% versus 8.4%), cardiogenic shock (11.5% versus 6.4%), and use of mechanical circulatory support (19.8% versus 18.7%). In-hospital mortality in CABG admissions decreased from 5.3% (2000) to 3.6% (2017) (adjusted OR, 0.89; 95% CI, 0.88-0.89 [P<0.001]) in the overall cohort, with similar temporal trends in patients with ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction. An increase in lengths of hospital stay and hospitalization costs was seen over time. Conclusions Utilization of CABG has decreased substantially in acute myocardial infarction admissions, especially in patients with ST-segment-elevation myocardial infarction. Despite an increase in acuity and multiorgan failure, in-hospital mortality consistently decreased in this population.

Positron emission tomography objective parameters for assessment of left ventricular assist device infection using 18F-FDG PET/CT.

Left ventricular assist device (LVAD) is a life-saving therapy, but it poses a substantial infection risk. Current evaluation of LVAD infection with 18F-FDG PET/CT is predominately subjective. We present qualitative and semi-quantitative 18F-FDG PET/CT parameters for early detection of LVAD infection and site localization. We retrospectively reviewed all 25 LVAD patients at our institution who had undergone 18F-FDG PET/CT imaging between 2014 and 2018. LVADs were subdivided into five assessed regions: driveline exit site, subcutaneous driveline, LVAD pump, LVAD inflow, and LVAD outflow cannulae. Ultimate diagnosis of LVAD infection was determined by a multidisciplinary primary care team. Qualitative and semi-quantitative analysis of PET/CT data were performed, including calculation of the standardized uptake value maximum, mean, and peak (SUVmax, SUVmean, and SUVpeak, respectively), as well as metabolic tumor volume (MTV), and total lesion glycolysis (TLG). A total of 14 patients presented with symptoms of infection, and LVAD infection was ultimately diagnosed in 19 of the 25 cases. All cases were correctly identified on 18F-FDG PET/CT with no false positive and no false negative cases, corresponding to a sensitivity and specificity of 100%. The mean SUVmax range at noninfected sites was 2.5-3.4, and the range was 5.7-8.1 at infected sites, resulting in a significant difference (P < 0.01) at all LVAD regions. 18F-FDG PET/CT is a useful adjunctive tool for assessment of LVAD infection and infection localization, which is crucial for clinical management. A cut-off SUVmax 5 is recommended to help diagnose LVAD infection.

Ventricular tachycardia and preload deficiency post LVAD - The importance of integrated assessment.

Ventricular tachycardia (VT) is common in LVAD recipients, and although often well tolerated, may result in symptoms and ICD therapies, and therefore require further evaluation and treatment. However, preload deficiency may also contribute to the development of ventricular tachycardia after LVAD implantation by provoking inflow cannula related VT. In this report, three cases are described where ventricular tachycardia was evaluated by integrated assessment utilizing echo and the HeartWare HVAD console, and successfully treated by modification of LV loading conditions.

Non-invasive assessment of arterial pulsatility in patients with continuous-flow left ventricular assist devices.

INTRODUCTION: Long-term use of continuous-flow left ventricular assist devices may have negative consequences for autonomic, cardiovascular and gastrointestinal function. It has thus been suggested that non-invasive monitoring of arterial pulsatility in patients with a left ventricular assist device is highly important for ensuring patient safety and longevity. We have developed a novel, semi-automated frequency-domain-based index of arterial pulsatility that is obtained during suprasystolic occlusions of the upper arm: the 'cuff pulsatility index'. PURPOSE: The purpose of this study was to evaluate the relationship between the cuff pulsatility index and invasively determined arterial pulsatility in patients with a left ventricular assist device. METHODS: Twenty-three patients with a left ventricular assist device with end-stage heart failure (six females: age = 65 ± 9 years; body mass index = 30.5 ± 3.7 kg m-2) were recruited for this study. Suprasystolic occlusions were performed on the upper arm of the patient's dominant side, from which the cuff pressure waveform was obtained. Arterial blood pressure was obtained from the radial artery on the contralateral arm. Measurements were obtained in triplicate. The relationship between the cuff pressure and arterial blood pressure waveforms was assessed in the frequency-domain using coherence analysis. A mixed-effects approach was used to assess the relationship between cuff pulsatility index and invasively determined arterial pulsatility (i.e. pulse pressure). RESULTS: The cuff pressure and arterial blood pressure waveforms demonstrated a high coherence up to the fifth harmonic of the cardiac frequency (heart rate). The cuff pulsatility index accurately tracked changes in arterial pulse pressure within a given patient across repeated measurements. CONCLUSIONS: The cuff pulsatility index shows promise as a non-invasive index for monitoring residual arterial pulsatility in patients with a left ventricular assist device across time.

Trends, Predictors, and Outcomes of Temporary Mechanical Circulatory Support for Postcardiac Surgery Cardiogenic Shock.

Postcardiac surgery cardiogenic shock (PCCS) is seen in 2% to 6% of patients who undergo cardiac surgery. There are limited large-scale data on the use of mechanical circulatory support (MCS) in these patients. This study sought to evaluate the in-hospital mortality, trends, and resource utilization for PCCS admissions with and without MCS. A retrospective cohort of PCCS between 2005 and 2014 with and without the use of temporary MCS was identified from the National Inpatient Sample. Admissions for permanent MCS and heart transplant were excluded. Propensity-matching for baseline characteristics was performed. The primary outcome was in-hospital mortality and secondary outcomes included trends in use, hospital costs and lengths of stay. In the period between 2005 and 2014, there were 132,485 admissions with PCCS, with 51.3% requiring MCS. The intra-aortic balloon pump was the predominant device used with a steady increase in other devices. MCS use for more frequent in younger patients, males and those with higher co-morbidity. There was a decrease in MCS use across all demographic categories and hospital characteristics over time. Older age, female sex, previous cardiovascular morbidity and MCS use were independently predictive of higher in-hospital mortality. In 6,830 propensity-matched pairs, PCCS admissions that required MCS use, had higher in-hospital mortality (odds ratio 2.4; p<0.001), higher hospital costs ($98,759 ± 907 vs $81,099 ± 698; p<0.001) but not a longer length of stay compared with those without MCS use. In conclusion, in patients with PCCS, this study noted a steady decrease in MCS use. Use of MCS identified PCCS patients at higher risk for in-hospital mortality and greater resource utilization.

Pulmonary function assessment post-left ventricular assist device implantation.

AIM: The lungs-and particularly the alveolar-capillary membrane-may be sensitive to continuous flow (CF) and pulmonary pressure alterations in heart failure (HF). We aimed to investigate long-term effects of CF pumps on respiratory function. METHODS AND RESULTS: We conducted a retrospective study of patients with end-stage HF at our institution. We analysed pulmonary function tests [e.g. forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1 )] and diffusing capacity of the lung for carbon monoxide (DLCO ) from before and after left ventricular assist device (LVAD) implantation and compared them with invasive haemodynamic studies. Of the 274 patients screened, final study analysis involved 44 patients with end-stage HF who had CF LVAD implantation between 1 February 2007 and 31 December 2015 at our institution. These patients [mean (standard deviation, SD) age, 50 (9) years; male sex, n = 33, 75%] received either the HeartMate II (Thoratec Corp.) pump (77%) or the HeartWare (HeartWare International Inc.) pump. The mean (SD) left ventricular ejection fraction was 21% (13%). At a median of 237 days post-LVAD implantation, we observed significant DLCO decrease (-23%) since pre-implantation (P < 0.001). ΔDLCO had an inverse relationship with changes in pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) from pre-LVAD to post-LVAD implantation: ΔDLCO to ΔPCWP (r = 0.50, P < 0.01) and ΔDLCO to ΔRAP (r = 0.39, P < 0.05). We observed other reductions in FEV1 , FVC, and FEV1 /FVC between pre-LVAD and post-LVAD implantation. In mean (SD) values, FEV1 changed from 2.3 (0.7) to 2.1 (0.7) (P = 0.005); FVC decreased from 3.2 (0.8) to 2.9 (0.9) (P = 0.01); and FEV1 /FVC went from 0.72 (0.1) to 0.72 (0.1) (P = 0.50). Landmark survival analysis revealed that ΔDLCO from 6 months after LVAD implantation was predictive of death for HF patients [hazard ratio (95% confidence interval), 0.60 (0.28-0.98); P = 0.03]. CONCLUSIONS: Pulmonary function did not improve after LVAD implantation. The degree of DLCO deterioration is related to haemodynamic status post-LVAD implantation. The ΔDLCO within 6 months post-operative was associated with survival.

Hemodynamic Assessment of Patients With and Without Heart Failure Symptoms Supported by a Continuous-Flow Left Ventricular Assist Device.

OBJECTIVE: To investigate differences in invasive hemodynamic parameters and outcomes in patients with and without heart failure (HF) symptoms after left ventricular assist device (LVAD) implantation. PATIENTS AND METHODS: We performed a single-center retrospective analysis of 51 symptomatic patients and 50 patients with resolved HF symptoms who underwent right-sided heart catheterization (RHC) after LVAD implantation from March 1, 2007, through June 30, 2016. Patient characteristics and outcomes including all-cause mortality and right ventricular (RV) failure were compared between groups. RESULTS: Fifty-one patients had development of HF symptoms after LVAD implantation and underwent RHC a mean ± SD of 243.7±288 days postoperatively. Fifty asymptomatic LVAD recipients underwent routine RHC 278.6±205 days after implantation. Compared with patients who had resolved HF symptoms, symptomatic patients were older, more likely to be male, and more likely to have ischemic cardiomyopathy. Symptomatic patients had higher right atrial pressure (P<.001), mean pulmonary arterial pressure (P<.001), and pulmonary capillary wedge pressure (P<.001). Improvements in right atrial pressure, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure before and after LVAD implantation were less remarkable in symptomatic patients. The frequency of RV dysfunction was significantly higher among symptomatic patients than patients with resolved HF symptoms (P=.001). Symptomatic patients displayed significantly higher risk of all-cause mortality (hazard ratio, 3.0; 95% CI, 1.3-6.5; P=.007) and RV failure (hazard ratio, 6.2; 95% CI, 1.3-29.7; P=.02) independent of other predictors of outcome. CONCLUSION: Patients with recurrent HF symptoms after LVAD implantation display more profound hemodynamic derangements, greater burden of RV failure, and increased rates of all-cause mortality compared with LVAD recipients with resolved HF symptoms.

Basic Cardiac Surgery Skills on Sale for $22.50: An Aortic Anastomosis Simulation Curriculum.

BACKGROUND: Current resident and student duty-hour restrictions necessitate efficient training, which may be aided by simulation. Data on the utility of low-cost simulation in cardiothoracic surgery are scant. We evaluated the effect and value of a low-cost, low-fidelity aortic anastomosis simulation curriculum. METHODS: Twenty participants (11 medical students, 9 residents) completed an aortic anastomosis on a porcine heart as a pretest. Participants were then provided access to a 14-minute online video created by a cardiac surgeon and given a low-cost task trainer for self-directed practice. Five weeks later, participants performed another aortic anastomosis on a porcine heart as a posttest. Pretest and posttest performances were filmed, deidentified, and graded blindly and independently by two cardiac surgeons using a standardized assessment tool (perfect score, 110; passing score, 58 or higher). Participants were surveyed anonymously after the posttest. RESULTS: The mean (SD) aortic anastomosis performance score improved significantly from pretest (53.3 [25.3]) to posttest (83.6 [15.3]; p < 0.001). Pass rates also improved significantly (35% versus 95%, p < 0.001). Medical students' scores improved most (p = 0.01). All 20 participants reported improved confidence in performing the task, and 18 believed that the online video was essential to better performance. The cost of the curriculum totaled $22.50 per participant, with 6 hours of total staff time required for assessment. CONCLUSIONS: An aortic anastomosis training and simulation curriculum improves the skills of student and resident trainees with minimal expense and staff time commitment. Such a curriculum may be of great value to both cardiothoracic training programs and their trainees.

Use of Post-acute Care Services and Readmissions After Left Ventricular Assist Device Implantation in Privately Insured Patients.

BACKGROUND: Very little is known about health care resource utilization, including post-acute care use and hospital readmissions, after left ventricular assist device (LVAD) implantation. METHODS AND RESULTS: Administrative claims from a database of multiple United States health plans were used to identify patients that received an LVAD (ICD-9 code 37.66) and survived to hospital discharge from January 1-2006, through September 30-2013. Post-acute care use was defined as a skilled nursing facility or rehabilitation stay within 90 days after hospital discharge. Patients were censored at heart transplantation or end of coverage through December 31-2013. Of 583 patients (mean age 55 years, 77% male), 223 (38.3%) used post-acute care services, more commonly in patients with diabetes, who required hemodialysis, and who had LVADs implanted at hospitals in more populated areas, with more beds, and in the northeast region (P < .05 for each). The most common reasons for readmission were device complications, heart failure, and arrhythmia. Readmission risk was higher in patients who had diabetes, peripheral vascular disease, and longer hospital length of stay, but it did not differ by post-acute care use. CONCLUSIONS: Use of post-acute care services varies based on hospital characteristics. We found no association between post-acute care use and readmission risk after LVAD implantation.

Assessment of coronary artery disease risk in 5463 patients undergoing cardiac surgery: when is preoperative coronary angiography necessary?

OBJECTIVES: We sought to critically analyze the routine use of conventional coronary angiography (CCA) before noncoronary cardiac surgery and to assess clinical prediction models that might allow more selective use of CCA in this setting. METHODS: We studied 5463 patients undergoing aortic valve surgery, mitral valve surgery, or septal myectomy with or without coronary artery bypass grafting from 2001 to 2010. Preoperative CCAs were evaluated for the presence of significant coronary artery disease (CAD). Random forests and logistic regression methods were used to determine the predictors of significant (≥50%) coronary stenosis. RESULTS: Preoperative CCA was performed in 4711 patients (86%). Two thirds of those with angina, previous myocardial infarction, or percutaneous coronary intervention had significant CAD found on CCA, versus one third of patients free of these risk factors (P < .001). Among 3019 patients without angina, previous myocardial infarction or percutaneous coronary intervention, older age, male gender, diabetes, and peripheral vascular disease independently predicted significant CAD (P < .001 for all; C-index = 0.74). Specifically, a multivariate model with these variables identified 10% (301 of 3019) of patients as having a low (≤10%) probability of coronary stenosis, of whom fewer than 5% had significant CAD and fewer than 1% had left main or triple-vessel coronary disease. CONCLUSIONS: In the absence of angina, previous myocardial infarction, or percutaneous coronary intervention, preoperative CCA identified significant CAD in only one third of patients. Our clinical prediction models could enhance the identification of patients at low risk of significant CAD for whom CCA might potentially be avoided before cardiac surgery. This strategy may improve the efficiency of cardiac surgical care delivery by diminishing procedure-related morbidity and offering significant cost savings.

Management of advanced heart failure in the elderly: ethics, economics, and resource allocation in the technological era.

Significant strides have been made in the durability, portability, and safety of mechanical circulatory support devices (MCS). Although transplant is considered the standard treatment for advanced heart failure, limits in organ availability leave a much larger pool of recipients in need versus donors. MCS is used as bridge to transplantation and as destination therapy (DT) for patients who will have MCS as their final invasive therapy with transplant not being an option. Despite improvements in quality of life (QOL) and survival, defining the optimal candidate for DT may raise questions regarding the economics of this approach as well as ethical concerns regarding just distribution of goods and services. This paper highlights some of the key ethical issues related to justice and the costs of life-prolonging therapies with respect to resource allocations. Available literature, current debates, and future directions are discussed herein.