Predicting in-hospital mortality among patients admitted with a diagnosis of heart failure: a machine learning approach.

Existing risk prediction models for hospitalized heart failure patients are limited. We identified patients hospitalized with a diagnosis of heart failure between 7 May 2013 and 26 April 2022 from a large academic, quaternary care medical centre (training cohort). Demographics, medical comorbidities, vitals, and labs were collected and were used to construct random forest machine learning models to predict in-hospital mortality. Models were compared with logistic regression, and to commonly used heart failure risk scores. The models were subsequently validated in patients hospitalized with a diagnosis of heart failure from a second academic, community medical centre (validation cohort). The entire cohort comprised 21 802 patients, of which 14 539 were in the training cohort and 7263 were in the validation cohort. The median age (25th-75th percentile) was 70 (58-82) for the entire cohort, 43.2% were female, and 6.7% experienced inpatient mortality. In the overall cohort, 7621 (35.0%) patients had heart failure with reduced ejection fraction (EF ≤ 40%), 1271 (5.8%) had heart failure with mildly reduced EF (EF 41-49%), and 12 910 (59.2%) had heart failure with preserved EF (EF ≥ 50%). Random forest models in the validation cohort demonstrated a c-statistic (95% confidence interval) of 0.96 (0.95-0.97), sensitivity (SN) of 87.3%, and specificity (SP) of 90.6% for the prediction of in-hospital mortality. Models for those with HFrEF demonstrated a c-statistic of 0.96 (0.94-0.98), SN 88.2%, and SP 91.0%, and those for patients with HFpEF showed a c-statistic of 0.95 (0.93-0.97), SN 87.4%, and SP 89.5% for predicting in-hospital mortality. The random forest model significantly outperformed logistic regression (c-statistic 0.87, SN 75.9%, and SP 86.9%), and current existing risk scores including the Acute Decompensated Heart Failure National Registry risk score (c-statistic of 0.70, SN 69%, and SP 62%), and the Get With the Guidelines-Heart Failure risk score (c-statistic 0.69, SN 67%, and SP 63%); P < 0.001 for comparison. Machine learning models built from commonly recorded patient information can accurately predict in-hospital mortality among patients hospitalized with a diagnosis of heart failure.

Early Utilization of Mechanical Circulatory Support in Acute Myocardial Infarction Complicated by Cardiogenic Shock: The National Cardiogenic Shock Initiative.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is associated with significant morbidity and mortality. Mechanical circulatory support (MCS) devices increase systemic blood pressure and end organ perfusion while reducing cardiac filling pressures. METHODS AND RESULTS: The National Cardiogenic Shock Initiative (NCT03677180) is a single-arm, multicenter study. The purpose of this study was to assess the feasibility and effectiveness of utilizing early MCS with Impella in patients presenting with AMI-CS. The primary end point was in-hospital mortality. A total of 406 patients were enrolled at 80 sites between 2016 and 2020. Average age was 64±12 years, 24% were female, 17% had a witnessed out-of-hospital cardiac arrest, 27% had in-hospital cardiac arrest, and 9% were under active cardiopulmonary resuscitation during MCS implantation. Patients presented with a mean systolic blood pressure of 77.2±19.2 mm Hg, 85% of patients were on vasopressors or inotropes, mean lactate was 4.8±3.9 mmol/L and cardiac power output was 0.67±0.29 watts. At 24 hours, mean systolic blood pressure improved to 103.9±17.8 mm Hg, lactate to 2.7±2.8 mmol/L, and cardiac power output to 1.0±1.3 watts. Procedural survival, survival to discharge, survival to 30 days, and survival to 1 year were 99%, 71%, 68%, and 53%, respectively. CONCLUSIONS: Early use of MCS in AMI-CS is feasible across varying health care settings and resulted in improvements to early hemodynamics and perfusion. Survival rates to hospital discharge were high. Given the encouraging results from our analysis, randomized clinical trials are warranted to assess the role of utilizing early MCS, using a standardized, multidisciplinary approach.

Exploring the relationship between epigenetic DNA methylation and cardiac fibrosis through Raman microspectroscopy.

Cardiomyopathies are associated with fibrotic remodeling of the heart, which is characterized by the excessive accumulation of collagen type I (COL I) due to chronic inflammation and suspected epigenetic influences. Despite the severity and high mortality rate of cardiac fibrosis, current treatment options are often inadequate, underscoring the importance of gaining a deeper understanding of the disease's underlying molecular and cellular mechanisms. In this study, the extracellular matrix (ECM) and nuclei in fibrotic areas of different cardiomyopathies were molecularly characterized by Raman microspectroscopy and imaging and compared with the control myocardium. Patient samples were obtained from heart tissue affected by ischemia, hypertrophy, and dilated cardiomyopathy and analyzed for fibrosis through conventional histology and marker-independent Raman microspectroscopy (RMS). Prominent differences between control myocardium and cardiomyopathies were revealed by spectral deconvolution of COL I Raman spectra. Statistically significant differences were identified in the amide I region of spectral subpeak at 1,608 cm-1, which is a representative endogenous marker for alterations in the structural conformation of COL I fibers. Moreover, epigenetic 5mC DNA modification was identified within cell nuclei by multivariate analysis. A statistically significant increase in signal intensities of spectral features indicative of DNA methylation was detected in cardiomyopathies in accordance with immunofluorescence 5mC staining. Overall, RMS is a versatile technology in the discrimination of cardiomyopathies based on molecular evaluation of COL I and nuclei while providing insights into the pathogenesis of the diseases.NEW & NOTEWORTHY Cardiomyopathies are associated with severe fibrotic remodeling of the heart, which is characterized by the excessive accumulation of collagen type I (COL I). In this study, we used marker-independent Raman microspectroscopy (RMS) to gain a deeper understanding of the disease's underlying molecular and cellular mechanisms.

Outcomes in orthotopic heart transplantation following pacemaker implantation.

BACKGROUND: Bradyarrhythmias including sinus node dysfunction (SND) and atrioventricular block (AVB) can necessitate pacemaker (PPM) implantation in orthotopic heart transplant (OHT) recipients. Prior studies have shown conflicting findings regarding the effect of PPM implantation on survival. We evaluated the effect of PPM indication on long-term re-transplant-free survival in OHT patients. METHODS: We conducted a retrospective cohort study of OHT patients at UCLA Medical Center from 1985 to 2018. Indication for PPM (SND, AVB) was identified. Cox proportional hazards model with pacemaker implantation as a time-varying covariate was used to evaluate its effect on the primary endpoint of retransplant or death. We included 1609 OHTs in 1511 adult patients with median follow-up of 12 years. RESULTS: At transplant, patients were aged 53 ± 13 years and 1125 (74.5%) were male. Pacemakers were implanted in 109 (7.2%) patients; 65 for SND (4.3%) and 43 for AVB (2.8%). Repeat OHT was performed in 103 (6.4%) cases and 798 (52.8%) patients died during the follow-up period. The risk of the primary endpoint was significantly higher in patients requiring PPM for AVB (HR 3.0, 95% CI 2.1-4.2, p < .01) after controlling for age at OHT, gender, hypertension, diabetes, renal disease, history of repeat OHT, acute rejection, transplant coronary vasculopathy, and atrial fibrillation, but not PPM for SND (HR 1.0, 95% CI 0.70-1.4, p = 1.0). CONCLUSIONS: Patients who required PPM for AVB, but not SND, were at significantly higher risk of death or retransplant compared to patients who did not require PPM.

Raman microspectroscopy identifies fibrotic tissues in collagen-related disorders via deconvoluted collagen type I spectra.

Fibrosis is a consequence of the pathological remodeling of extracellular matrix (ECM) structures in the connective tissue of an organ. It is often caused by chronic inflammation, which over time, progressively leads to an excess deposition of collagen type I (COL I) that replaces healthy tissue structures, in many cases leaving a stiff scar. Increasing fibrosis can lead to organ failure and death; therefore, developing methods that potentially allow real-time monitoring of early onset or progression of fibrosis are highly valuable. In this study, the ECM structures of diseased and healthy human tissue from multiple organs were investigated for the presence of fibrosis using routine histology and marker-independent Raman microspectroscopy and Raman imaging. Spectral deconvolution of COL I Raman spectra allowed the discrimination of fibrotic and non-fibrotic COL I fibers. Statistically significant differences were identified in the amide I region of the spectral subpeak at 1608 cm-1, which was deemed to be representative for structural changes in COL I fibers in all examined fibrotic tissues. Raman spectroscopy-based methods in combination with this newly discovered spectroscopic biomarker potentially offer a diagnostic approach to non-invasively track and monitor the progression of fibrosis. STATEMENT OF SIGNIFICANCE: Current diagnosis of fibrosis still relies on histopathological examination with invasive biopsy procedures. Although, several non-invasive imaging techniques such as positron emission tomography, single-photon emission computed tomography and second harmonic generation are gradually employed in preclinical or clinical studies, these techniques are limited in spatial resolution and the morphological interpretation highly relies on individual experience and knowledge. In this study, we propose a non-destructive technique, Raman microspectroscopy, to discriminate fibrotic changes of collagen type I based on a molecular biomarker. The changes of the secondary structure of collagen type I can be identified by spectral deconvolution, which potentially can provide an automatic diagnosis for fibrotic tissues in the clinical applicaion.

Outcomes of heart transplant recipients bridged with percutaneous versus durable left ventricular assist devices.

BACKGROUND: The new United Network for Organ Sharing (UNOS) heart allocation policy prioritizes temporary percutaneous over durable left ventricular assist devices (LVAD) as bridge to transplant. We sought to examine 1-year outcomes of heart transplant recipients bridged with Impella versus durable LVADs. METHODS: All primary adult orthotopic heart transplant recipients registered in UNOS between January 2016 and June 2021 were analyzed. Recipients were identified as being bridged with isolated durable or percutaneous LVAD at the time of transplant. Baseline characteristics were compared and 1-year survival was examined using the Kaplan Meier method and multivariable Cox proportional hazards regression. RESULTS: During our study period, heart transplant recipients bridged with LVADs were divided between 5422(94%) durable and 324(6%) percutaneous options. Impella-bridged recipients were more likely to be status 1A under the old allocation system (98% vs. 70%, p < .01) and status 2 or higher under the new allocation system (99% vs. 24%, p < .01). Impella-bridged recipients were less likely to be obese (27% vs. 42%, p < .01), have ischemic cardiomyopathy (27% vs. 34%, p < .01), and were more likely to be on inotropic agents at the time of transplant (68% vs. 6%, p < .01). One-year post-transplant survival was not significantly different between the two groups on univariable (HR .87, 95% CI .56-1.37) or multivariable analysis (aHR .63, 95% CI .37-1.07). CONCLUSIONS: Following the UNOS allocation policy change, Impella utilization has increased with no significant difference in 1-year survival compared to bridge with durable LVADs. Impella may be a reasonable alternative to durable LVADs in select patients.

Characteristics and outcomes of patients presenting with acute myocardial infarction and cardiogenic shock during COVID-19.

OBJECTIVES: To evaluate characteristics and outcomes of patients presenting with acute myocardial infarction and cardiogenic shock (AMICS) during the coronavirus disease 2019 (COVID-19) pandemic. BACKGROUND: The COVID-19 pandemic has created challenges in delivering acute cardiovascular care. Quality measures and outcomes of patients presenting with AMICS during COVID-19 in the United States have not been well described. METHODS: We identified 406 patients from the National Cardiogenic Shock Initiative (NCSI) with AMICS and divided them into those presenting before (N = 346, 5/9/2016-2/29/2020) and those presenting during the COVID-19 pandemic (N = 60, 3/1/2020-11/10/2020). We compared baseline clinical data, admission characteristics, and outcomes. RESULTS: The median age of the cohort was 64 years, and 23.7% of the group was female. There were no significant differences in age, sex, and medical comorbidities between the two groups. Patients presenting during the pandemic were less likely to be Black compared to those presenting prior. Median door to balloon (90 vs. 88 min, p = 0.38), door to support (88 vs. 78 min, p = 0.13), and the onset of shock to support (74 vs. 62 min, p = 0.15) times were not significantly different between the two groups. Patients presented with ST-elevation myocardial infarction more often during the COVID-19 period (95.0% vs. 80.0%, p = 0.005). In adjusted logistic regression models, COVID-19 period did not significantly associate with survival to discharge (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.54-2.19, p = 0.81) or with 1-month survival (OR 0.82, 95% CI 0.42-1.61, p = 0.56). CONCLUSIONS: Care of patients presenting with AMICS has remained robust among hospitals participating in the NCSI during the COVID-19 pandemic.

Early trends in cardiac allograft vasculopathy after implementation of the 2018 donor heart allocation policy in the United States.

STUDY OBJECTIVE: To evaluate the impact of the new donor heart allocation system implemented in the United States in October 2018 on development of early cardiac allograft vasculopathy (CAV). DESIGN: Retrospective cohort study. PARTICIPANTS: Adult (≥ 18 years) heart transplant recipients registered in the United Network for Organ Sharing database between October 18, 2015 and October 17, 2018 (old system) and October 18, 2018 and May 31, 2020 (new system). MAIN OUTCOME MEASURE: Incidence of angiographic CAV at 1 year (accelerated CAV) in the overall transplant population and among the highest acuity subgroup-Status 1A (old) and Status 1 or 2 (new). We included recipient and donor demographic, cardiovascular, and transplant factors in multivariable logistic regression models to identify predictors of accelerated CAV. RESULTS: Of 10,375 transplant recipients, 6,660 (64%) and 3,715 (36%) were listed in the old and new allocation cohorts, respectively. The incidence of accelerated CAV was 521 (8%) in the old period compared with 272 (7%) in the new period (P = .36). Similar incidence rates were observed in the highest acuity subgroup-363 (8%) compared with 143 (7%), respectively (P = .13). In adjusted analyses of the high-acuity cohort, the new allocation system was not associated with a higher likelihood of accelerated CAV (odds ratio = 0.87, 95% confidence interval: 0.70-1.08, P = .20). CONCLUSIONS: The new donor heart allocation system is not associated with development of accelerated angiographic CAV at 1 year, including among recipients requiring the most urgent transplants.

Hemodynamic effects of COVID-19 vaccination in hospitalized patients awaiting heart transplantation.

Background: The hemodynamic effects of pre-transplant vaccination against COVID-19 among heart transplant candidates hospitalized for advanced heart failure remains unknown. Methods: A retrospective chart review was conducted at a high-volume transplant center from January through December 2021. 22 COVID-19 vaccination events occurred among patients hospitalized for decompensated heart failure while awaiting transplantation. Primary outcomes included inotrope and vasopressor dosages. Secondary outcomes included vital signs, pulmonary artery catheter measurements, diuretic dosages, and renal function. Data were extracted 24 h before through 72 h after vaccination. Results: One of 22 vaccination events was associated with hemodynamic changes requiring increased inotropic and vasopressor support post-vaccination. In all other cases, transient hemodynamic changes occurred without need for escalated therapy. Conclusions: COVID-19 vaccination can be administered safely to most critically ill patients with advanced heart failure including those awaiting transplantation. All patients should be monitored closely as some may be susceptible to significant hemodynamic changes.

Implementation and outcomes of an urban mobile adult extracorporeal life support program.

Objective: Although extracorporeal life support (ECLS) has been increasingly adopted as rescue therapy for cardiac and pulmonary failure, it remains limited to specialized centers. The present study reports our institutional experience with mobile ECLS across broad indications, including postcardiotomy syndrome, cardiogenic shock, and COVID-19 acute respiratory failure. Methods: We performed a retrospective review of all patients transported to our institution through our mobile ECLS program from January 1, 2018, to January 15, 2021. Results: Of 110 patients transported to our institution on ECLS, 65.5% required venovenous, 30.9% peripheral venoarterial, and 3.6% central venoarterial support. The most common indications for mobile ECLS were acute respiratory failure (46.4%), COVID-19-associated respiratory failure (19.1%), cardiogenic shock (18.2%) and postcardiotomy syndrome (11.8%). The median pre-ECLS Pao2:Fio2 for venovenous-ECLS was 64 mm Hg (interquartile range [IQR], 53-75 mm Hg) and 95.8 mm Hg (IQR, 55-227 mm Hg) for venoarterial-ECLS, whereas median pH and base deficit were 7.25 (IQR, 7.16-7.33) and 7 mmol/L (IQR, 4-11 mmol/L) for those requiring venoarterial-ECLS. Patients were transported using a ground ambulance from 50 institutions with a median distance of 27.5 miles (IQR, 18.7-48.0 miles). Extracorporeal circulation was established within a median of 45 minutes (IQR, 30-55 minutes) after team arrival. Survival to discharge was 67.3% for those requiring venovenous-ECLS for non-COVID-19 respiratory failure, 52.4% for those with COVID-19%, and 54.1% for those requiring venoarterial-ECLS. Conclusions: Patients can be safely and expeditiously placed on ECLS across broad indications, utilizing ground transportation in an urban setting. Clinical outcomes are promising and comparable to institutional non-transfers and those reported by Extracorporeal Life Support Organization.

The Impact of Transitioning From In-Person to Virtual Heart Transplantation Selection Committee Meetings: Observational Study.

BACKGROUND: Heart transplant selection committee meetings have transitioned from in-person to remote video meetings during the COVID-19 pandemic, but how this impacts committee members and patient outcomes is unknown. OBJECTIVE: The aim of this study is to determine the perceived impact of remote video transplant selection meetings on usability and patient care and to measure patient selection outcomes during the transition period from in-person to virtual meetings. METHODS: A 35-item anonymous survey was developed and distributed electronically to the heart transplant selection committee. We reviewed medical records to compare the outcomes of patients presented at in-person meetings (January-March 2020) to those presented during video meetings (March-June 2020). RESULTS: Among 83 committee members queried, 50 were regular attendees. Of the 50 regular attendees, 24 (48%) were physicians and 26 (52%) were nonphysicians, including nurses, social workers, and coordinators; 46 responses were received, 23 (50%) from physicians and 23 (50%) from nonphysicians, with 41 responses fully completed. Overall, respondents were satisfied with the videoconference format and felt that video meetings did not impact patient care and were an acceptable alternative to in-person meetings. However, 54% (22/41) preferred in-person meetings, with 71% (15/21) of nonphysicians preferring in-person meetings compared to only 35% (7/20) of physicians (P=.02). Of the 46 new patient evaluations presented, there was a statistically nonsignificant trend toward fewer patients initially declined at video meetings compared with in-person meetings (6/24, 25% compared to 10/22, 45%; P=.32). CONCLUSIONS: The transition from in-person to video heart transplant selection committee meetings was well-received and did not appear to affect committee members' perceived ability to deliver patient care. Patient selection outcomes were similar between meeting modalities.

Fractional Flow Reserve in End-Stage Liver Disease.

Fractional flow reserve (FFR) determines the functional significance of epicardial stenoses assuming negligible venous pressure (Pv) and microvascular resistance. However, these assumptions may be invalid in end-stage liver disease (ESLD) because of fluctuating Pv and vasodilation. Accordingly, all patients with ESLD who underwent right-sided cardiac catheterization and coronary angiography with FFR as part of their orthotopic liver transplantation evaluation between 2013 and 2018 were included in the present study. Resting mean distal coronary pressure (Pd)/mean aortic pressure (Pa), FFR, and Pv were measured. FFR accounting for Pv (FFR - Pv) was defined as (Pd - Pv)/(Pa - Pv). The hyperemic effect of adenosine was defined as resting Pd/Pa - FFR. The primary outcome was all-cause mortality at 1 year. In 42 patients with ESLD, 49 stenoses were interrogated by FFR (90% were <70% diameter stenosis). Overall, the median model for ESLD score was 16.5 (10.8 to 25.5), FFR was 0.87 (0.81 to 0.94), Pv was 8 mm Hg (4 to 14), FFR-Pv was 0.86 (0.80 to 0.94), and hyperemic effect of adenosine was 0.06 (0.02 to 0.08). FFR-Pv led to the reclassification of 1 stenosis as functionally significant. There was no significant correlation between the median model for ESLD score and the hyperemic effect of adenosine (R = 0.10). At 1 year, 13 patients had died (92% noncardiac in etiology), and patients with FFR ≤0.80 had significantly higher all-cause mortality (73% vs 17%, p = 0.001. In conclusion, in patients with ESLD who underwent orthotopic liver transplantation evaluation, Pv has minimal impact on FFR, and the hyperemic effect of adenosine is preserved. Furthermore, even in patients with the predominantly angiographically-intermediate disease, FFR ≤0.80 was an independent predictor of all-cause mortality.

Benefits of both physical assessment and electronic health record review to assess frailty prior to heart transplant.

INTRODUCTION: Frailty status affects outcomes after heart transplantation, but the optimal way to assess frailty prior to transplant remains unknown. METHODS: This single-center, observational study assessed 44 heart transplant candidates for frailty using three methods. The Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) were used as two physical assessments of frailty. The Frailty Risk Score (FRS) was used as a chart-review based assessment measuring 20 different biopsychosocial and functional components, including biomarkers, depression, cognitive impairment, and sleep. RESULTS: We determined the correlation between FRS, SPPB, and FFP and how each correlated with clinical outcomes. Of 44 participants, mean age was 60 years. FRS correlated with SPPB and FFP (P = .043, P < .001, respectively). Higher frailty as measured by SPPB and FRS was significantly associated with lack of achieving waitlist status (P = .022; P = .002) and not being transplanted (P = .026; P = .008). Higher frailty by SPPB and FFP was also associated with mortality (P = .010; P = .025). CONCLUSION: SPPB and chart-review FRS showed potential for predicting waitlist and transplant status of heart transplant candidates, while SPPB and FFP were associated with mortality. Additional studies may serve to validate these observations.

Evaluating factors of greater patient satisfaction with outpatient cardiology telehealth visits during the COVID-19 pandemic.

BACKGROUND: The impact of telehealth on cardiovascular care during the COVID-19 pandemic on patient satisfaction and factors associated with satisfaction are not well characterized. METHODS: We conducted a nonrandomized, prospective cross-sectional survey study for outpatient telehealth cardiovascular visits over a 169-day period utilizing a validated telehealth usability questionnaire. For each variable, patients were divided into 2 groups-1 with scores above the median, labeled "greater satisfaction," and the other with scores below the median, labeled "less satisfaction." RESULTS: A total of 13,913 outpatient telehealth encounters were successfully completed during the study period. A total of 7327 unique patients were identified and received a survey invitation; 5993 (81.8%) patients opened the invitation, and 1034 (14.1%) patients consented and completed the survey. Overall mean and median scores were 3.15 (standard deviation 0.74) and 3.37 (interquartile range 2.73-3.68) (maximum score 4.00). Greater satisfaction was noted among younger patients (mean age 63.3 ± 14.0 years, P = .005), female gender (46.3%, P = .007), non-White ethnicity (24.2% P = .006), self-identified early adopters and innovators of new technology (49.8%, P < .001), 1-way travel time greater than 1 hour (22.3%, P < .001), 1-way travel distance greater than 10 miles (49.0%, P < .001), patients needing child care arrangement (16.4%, P < .001), and history of orthotopic heart transplant (OHT) (5.1%, P = .04). CONCLUSION: Patients reported overall satisfaction with telehealth during the COVID-19 pandemic. Factors associated with patient convenience, along with female gender, younger age, and non-White ethnicity, correlated with greater satisfaction. Cardiovascular comorbidities did not correlate with greater satisfaction except for OHT. Further research into the impact of telehealth on patient satisfaction, safety, and clinical outcomes is needed.

Change in Invasively Measured Mean Pulmonary Artery Pressure After Transcatheter Mitral Valve Repair Is Associated With Heart Failure Readmission.

BACKGROUND: Pre-existing pulmonary hypertension is associated with poor outcomes after transcatheter mitral valve repair (TMVr) for mitral regurgitation (MR). However, the impact of an immediate change in mean pulmonary artery pressure (ΔmPAP) following TMVr on outcomes is unknown. METHODS: Patients who underwent TMVr from December 2015 to February 18, 2020 at our institution for symptomatic 3-4+ MR and who had invasive hemodynamics measured immediately pre- and post-TMVR were included. Multivariate Cox regression analysis was performed to examine the association of ΔmPAP (post-TMVr - pre-TMVr mPAP) with the primary endpoint of heart failure (HF) readmission at 1 year. Secondary endpoints included all-cause mortality and the composite endpoint of HF readmission or all-cause mortality at 1 year. RESULTS: Among 55 patients, 55% were men, mean age was 72 ± 14.2 years, and mean ΔmPAP was -1.4 ± 8.2 mm Hg. Overall, HF readmission occurred in 14 (25%), death in 10 (18%), and the composite endpoint in 20 (36%) patients. In multivariable analyses, higher ΔmPAP was significantly associated with HF readmission (hazard ratio (HR) = 1.10, 95% confidence interval (CI): 1.00 - 1.21; P = 0.04). ΔmPAP was not associated with death (HR = 1.04, 95% CI: 0.96 - 1.14; P = 0.33), though there was a numerical but statistically non-significant trend towards the composite endpoint (HR = 1.06, 95% CI: 1.00 - 1.13; P = 0.06) driven by HF readmission. CONCLUSION: Higher ΔmPAP immediately following TMVr was associated with increased HF readmission at 1 year. Larger prospective studies are needed to validate these data and further explore the utility of ΔmPAP as a novel hemodynamic parameter to predict post-TMVR outcomes.

Post-Acute COVID-19 Syndrome and the cardiovascular system: What is known?

Post-Acute COVID-19 Syndrome (PACS) is defined by persistent symptoms >3-4 weeks after onset of COVID-19. The mechanism of these persistent symptoms is distinct from acute COVID-19 although not completely understood despite the high incidence of PACS. Cardiovascular symptoms such as chest pain and palpitations commonly occur in PACS, but the underlying cause of symptoms is infrequently known. While autopsy studies have shown that the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rarely causes direct myocardial injury, several syndromes such as myocarditis, pericarditis, and Postural Orthostatic Tachycardia Syndrome have been implicated in PACS. Additionally, patients hospitalized with acute COVID-19 who display biomarker evidence of myocardial injury may have underlying coronary artery disease revealed by the physiological stress of SARS-CoV-2 infection and may benefit from medical optimization. We review what is known about PACS and the cardiovascular system and propose a framework for evaluation and management of related symptoms.

Nidogen-1 Mitigates Ischemia and Promotes Tissue Survival and Regeneration.

Ischemia impacts multiple organ systems and is the major cause of morbidity and mortality in the developed world. Ischemia disrupts tissue homeostasis, driving cell death, and damages tissue structure integrity. Strategies to heal organs, like the infarcted heart, or to replace cells, as done in pancreatic islet ß-cell transplantations, are often hindered by ischemic conditions. Here, it is discovered that the basement membrane glycoprotein nidogen-1 attenuates the apoptotic effect of hypoxia in cardiomyocytes and pancreatic ß-cells via the αvß3 integrin and beneficially modulates immune responses in vitro. It is shown that nidogen-1 significantly increases heart function and angiogenesis, while reducing fibrosis, in a mouse postmyocardial infarction model. These results demonstrate the protective and regenerative potential of nidogen-1 in ischemic conditions.

Orthotopic Heart and Combined Heart Liver Transplantation: the Ultimate Treatment Option for Failing Fontan Physiology.

Purpose of the Review: This is a comprehensive update on failing Fontan physiology and the role of heart and combined heart and liver transplantation in the current era. Recent Findings: Single ventricle physiology encompasses a series of rare congenital cardiac abnormalities that are characterized by absence of or hypoplasia of one ventricle. This effectively results in a single ventricular pumping chamber. These abnormalities are rarely compatible with long-term survival if left without surgical palliation in the first few years of life. Surgical treatment of single ventricle physiology has evolved over the past 60 years and is characterized by numerous creative innovations. These include the development of arteriopulmonary shunts, the evolution of partial cavopulmonary connections, and the eventual development of the "Fontan" operation. Regardless of the type of Fontan modification, the long-term consequences of the Fontan operation are predominantly related to chronic central venous hypertension and the multi-organ consequences thereof. Atrial arrhythmias can further compromise this circulation.Patients with single ventricle physiology represent a special sub-segment of congenital cardiac transplants and are arguably the most challenging patients considered for transplantation. Summary: This review describes in detail the challenges and opportunities of heart and liver transplantation in Fontan patients, as viewed and managed by the experienced team at the Ahmanson/UCLA Adult Congenital Heart Center.