Cardiac rehabilitation for heart failure: progress and gaps in evidence and policy.

PURPOSE OF REVIEW: This review synthesizes recent research on the efficacy, optimal design, and delivery methods of cardiac rehabilitation tailored to heart failure patients. Despite established benefits, cardiac rehabilitation referral and access disparities persist, necessitating elucidation of limitations and solutions. RECENT FINDINGS: Exercise-based cardiac rehabilitation improves long-term mortality and hospitalization rates but not short-term mortality. cardiac rehabilitation further enhances quality of life and medical therapy adherence. However, cardiac rehabilitation relies on in-person delivery, presenting access barriers exacerbated during COVID-19. Significant geographic disparities exist, with analyses indicating current capacity only serves 45% of eligible US adults even if fully utilized. Referral rates also lag, disproportionately affecting women and minority groups. Research increasingly focuses on home-based and digital therapeutics modalities to expand reach, with evidence demonstrating comparable improvements across settings. Protocols and research center on heart failure with reduced ejection fraction (HFrEF), despite growing heart failure with preserved ejection fraction (HFpEF) prevalence. SUMMARY: Increasing referrals through standardized procedures and addressing multifactorial geographic, economic, and capacity limitations are imperative to ensure equitable cardiac rehabilitation access. Broadening HFpEF rehabilitation research and care standards also constitutes a critical practice gap requiring alignment with projected epidemiologic shifts. Advancing patient-centered, evidence-based solutions can promote rehabilitation as essential secondary prevention for wider cardiac populations. VIDEO ABSTRACT: http://links.lww.com/HCO/A97.

Left ventricular hemodynamics with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: There is considerable debate about the hemodynamic effects of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). AIMS: To evaluate the changes in left ventricular (LV) function, volumes, and work in patients treated with VA-ECMO using invasive LV catheterization and three-dimensional echocardiographic volumes. METHODS: Patients on VA-ECMO underwent invasive hemodynamic evaluation due to concerns regarding candidacy for decannulation. Hemodynamic parameters were reported as means±standard deviations or medians (interquartile ranges) after evaluating for normality. Paired comparisons were done to evaluate hemodynamics at the baseline (highest) and lowest tolerated levels of VA-ECMO support. RESULTS: Twenty patients aged 52.3 ± 15.8 years were included. All patients received VA-ECMO for refractory cardiogenic shock (5/20 SCAI stage D, 15/20 SCAI stage E). At 3.0 (2.0, 4.0) days after VA-ECMO cannulation, the baseline LV ejection fraction was 20% (15%, 27%). The baseline and lowest VA-ECMO flows were 4.0 ± 0.6 and 1.5 ± 0.6 L/min, respectively. Compared to the lowest flow, full VA-ECMO support reduced LV end-diastolic volume [109 ± 81 versus 134 ± 93 mL, p = 0.001], LV end-diastolic pressure (14 ± 9 vs. 19 ± 9 mmHg, p < 0.001), LV stroke work (1858 ± 1413 vs. 2550 ± 1486 mL*mmHg, p = 0.002), and LV pressure-volume area (PVA) (4507 ± 1910 vs. 5193 ± 2388, p = 0.03) respectively. Mean arterial pressure was stable at the highest and lowest flows (80 ± 16 vs. 75 ± 14, respectively; p = 0.08) but arterial elastance was higher at the highest VA-ECMO flow (4.9 ± 2.2 vs lowest flow 2.7 ± 1.6; p < 0.001). CONCLUSIONS: High flow VA-ECMO support significantly reduced LV end-diastolic pressure, end-diastolic volume, stroke work, and PVA compared to minimal support. The Ea was higher and MAP was stable or minimally elevated on high flow.

Validation of the Minnesota Pectoralis Risk Score to predict mortality in the HeartMate 3 population.

BACKGROUND: The Minnesota Pectoralis Risk Score (MPRS) utilizes computed tomography-quantified thoracic muscle and clinical variables to predict survival after left ventricular assist device (LVAD) implantation. The model has not been prospectively tested in HeartMate 3 recipients. METHODS: A single-center HeartMate 3 cohort from July 2016 to July 2021 (n = 108) was utilized for this analysis. Cohort subjects with complete covariates for MPRS calculation (pectoralis muscle measures, Black race, creatinine, total bilirubin, body mass index, bridge to transplant status, and presence/absence of contrast) implanted after MPRS development were included. MPRS were calculated on each subject. Receiver operating characteristic curves were generated to test model discrimination at 30-day, 90-day, and 1-year mortality post-LVAD. Next, the performance of the 1-year post-LVAD outcome was compared to the HeartMate 3 survival risk score (HM3RS). RESULTS: The mean age was 58 (15 years), 80% (86/108) were male, and 26% (28/108) were destination therapy. The area under the curve (AUC) for the MPRS model to predict post-LVAD mortality was 0.73 at 30 days, 0.78 at 90 days, and 0.81 at 1 year. The AUC for the HM3RS for the 1-year outcome was 0.693. Each 1-unit point of the MPRS was associated with a significant increase in the hazard rate of death after LVAD (hazard ratio 2.1, 95% confidence interval 1.5-3.0, p < 0.0001). CONCLUSIONS: The MPRS had high performance in this prospective validation, particularly with respect to 90-day and 1-year post-LVAD mortality. Such a tool can provide additional information regarding risk stratification to aid informed decision-making.

Multicenter study of universal prophylaxis versus pre-emptive therapy for patients at intermediate risk (R+) for CMV following heart transplantation.

INTRODUCTION: Heart transplant (HT) recipients with prior exposure to cytomegalovirus (CMV R+) are considered intermediate risk for CMV-related complications. Consensus guidelines allow for either universal prophylaxis (UP) or preemptive therapy (PET) (serial CMV testing) approaches to CMV prevention in such patients. Whether an optimal approach to mitigate CMV related risks exists in this setting remains uncertain. We therefore assessed the utility of PET as compared to UP in CMV R+ HT recipients. METHODS: Retrospective analysis of all CMV R+ HT recipients from 6 U.S. centers between 2010 and 2018 was performed. The primary outcome was the development of CMV DNAemia or end-organ disease resulting in the initiation/escalation of anti-CMV therapy. The secondary outcome was CMV-related hospitalization. Additional outcomes included incidence of acute cellular rejection (ACR) ≥ grade 2R, death, cardiac allograft vasculopathy (CAV), and leukopenia. RESULTS: Of 563 CMV R+ HT recipients, 344 (61.1%) received UP. PET was associated with increased risk for the primary (adjusted HR 3.95, 95% CI: 2.65-5.88, p < .001) and secondary (adjusted HR 3.19, 95% CI: 1.47-6.94, p = .004) outcomes, and with increased ACR ≥ grade 2R (PET 59.4% vs. UP 34.4%, p < .001). Incidence of detectable CAV was similar at 1 year (PET 8.2% vs. UP 9.5%, p = .698). UP was associated with increased incidence of leukopenia within 6 months post-HT (PET 34.7% vs. UP 43.6%, p = .036). CONCLUSION: The use of a PET CMV prophylaxis strategy in intermediate risk HT recipients associated with increased risk of CMV infection and CMV-related hospitalization, and may associate with worse post-HT graft outcomes.

Association between calculated panel reactive antibody and waitlist outcomes in the 2018 heart allocation system.

BACKGROUND: The impact of heart transplant (HT) waitlist candidate sensitization on waitlist outcomes in the US is unknown. METHODS: Adult waitlist outcomes in OPTN (October 2018-September 2022) by calculated panel reactive antibody (cPRA) were modeled to identify thresholds of clinical significance. The primary outcome was the rate of HT by cPRA category (low: 0-35, middle: >35-90, high: >90) assessed using multivariable competing risk analysis (compete: waitlist removal for death or clinical deterioration). The secondary outcome was waitlist removal for death or clinical deterioration. RESULTS: The elevated cPRA categories were associated with lower rates of HT. Candidates in the middle (35-90) and high cPRA categories (>90) had an adjusted 24% lower rate (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.80-0.92) and 61% lower rate (HR 0.39 95% CI. 0.33-0.47) of HT than the lowest category, respectively. Waitlist candidates in the high cPRA category listed in the top acuity strata (Statuses 1, 2) had increased rates of delisting for death or deterioration compared to those in the low cPRA category (adjusted HR 2.9, 95% CI 1.5-5.5), however, elevated cPRA (middle, high) was not associated with an increased rate of death and delisting when the cohort was considered as a whole. CONCLUSIONS: Elevated cPRA was associated with reduced rates of HT across all waitlist acuity tiers. Among HT waitlist candidates listed at the top acuity strata, the high cPRA category was associated with increased rates of delisting due to death or deterioration. Elevated cPRA may require consideration for critically ill candidates under continuous allocation.

Sex-Specific Outcomes of Candidates Listed as the Highest Priority Status for Heart Transplantation.

BACKGROUND: While sex differences in heart transplantation (HT) waitlist mortality have been previously described, waitlist and HT outcomes by sex of patients in the highest urgency strata (Status 1) since implementation of the 2018 allocation system change in the United States are unknown. We hypothesized that women listed as Status 1 may have worse outcomes due to adverse events on temporary mechanical circulatory support. METHODS: The analysis included adult, single-organ HT waitlist candidates listed as Status 1 at any time while listed, after the HT allocation system change (from October 18, 2018 through March 31, 2022). The primary outcome was the rate of HT by sex, assessed using multivariable competing risk analysis where waitlist removal for death or clinical deterioration was the competing event. Post-HT survival by sex of waitlist candidates transplanted as a Status 1 was also compared. RESULTS: Of 1120 Status 1 waitlist candidates (23.8% women), women had a lower rate of HT compared to men (adjusted hazard ratio, 0.74 [95% CI, 0.62-0.88]; P<0.001) and a higher rate of delisting for death or medical unsuitability (adjusted hazard ratio, 1.48 [95% CI, 1.05-2.09]; P=0.026). Calculated panel reactive antibody did not account for all the harm observed. Post-HT survival of Status 1 candidates by sex was similar (adjusted hazard ratio, 1.13 [95% CI, 0.62-2.06]; P=0.70). CONCLUSIONS: Women have a lower rate of HT and higher rate of delisting for death or clinical deterioration at the highest urgent status, which appears to be mediated but not fully explained by calculated panel reactive antibody levels. Further investigation into the safety profile of temporary mechanical circulatory support devices in women is needed.

Temporary Mechanical Circulatory Support Use and Clinical Outcomes of Simultaneous Heart/Kidney Transplant Recipients in the Pre- and Post-heart Allocation Policy Change Eras.

BACKGROUND: The use of temporary mechanical circulatory support (tMCS) devices (intra-aortic balloon pump; Impella 2.5, CP, 5.0; venoarterial extracorporeal membrane oxygenation) increased significantly across the United States for heart transplant candidates after the allocation policy change. Whether this practice change also affected simultaneous heart-kidney (SHK) candidates and recipient survival is understudied. METHODS: We used the Scientific Registry of Transplant Recipients database to identify adult SHK recipients between January 2010 and March 2022. The population was stratified into pre- and post-heart allocation change cohorts. Kaplan-Meier curves were generated to compare 1-y survival rates. A Cox proportional hazards model was used to investigate the effect of allocation period on patient survival. Recipient outcomes bridged with eligible tMCS devices were compared in the post-heart allocation era. In a separate analysis, SHK waitlist mortality was evaluated between the allocation eras. RESULTS: A total of 1548 SHK recipients were identified, and 1102 were included in the final cohort (534 pre-allocation and 568 post-allocation change). tMCS utilization increased from 17.9% to 51.6% after the allocation change, with venoarterial extracorporeal membrane oxygenation use rising most significantly. However, 1-y post-SHK survival remained unchanged in the full cohort (log-rank P = 0.154) and those supported with any of the eligible tMCS devices. In a separate analysis (using a larger cohort of all SHK listings), SHK waitlist mortality at 1 y was significantly lower in the current allocation era ( P = 0.002). CONCLUSIONS: Despite the remarkable increase in tMCS use in SHK candidates after the heart allocation change, 1 y posttransplant survival remained unchanged. Further studies with larger cohorts and longer follow-ups are needed to confirm these findings.

Hypotension on cardiopulmonary stress test predicts 90 day mortality after LVAD implantation in INTERMACS 3-6 patients.

AIMS: Cardiopulmonary stress test (CPX) is routinely performed when evaluating patient candidacy for left ventricular assist device (LVAD) implantation. The predictive value of hypotensive systolic blood pressure (SBP) response during CPX on clinical outcomes is unknown. This study aims to determine the effect of hypotensive SBP response during to clinical outcomes among patients who underwent LVAD implantation. METHODS AND RESULTS: This was a retrospective single center study enrolling consecutive patients implanted with a continuous flow LVAD between 2011 and 2022. Hypotensive SBP response was defined as peak exercise SBP below the resting value. Multivariable Cox-regression analysis was performed to evaluate the relationship between hypotensive SBP response and all-cause mortality within 30 and 90 days of LVAD implantation. A subgroup analysis was performed for patients implanted with a HeartMate III (HM III) device. Four hundred thirty-two patients underwent LVAD implantation during the pre-defined period and 156 with INTERMACS profiles 3-6 met our inclusion criteria. The median age was 63 years (IQR 54-69), and 52% had ischaemic cardiomyopathy. Hypotensive SBP response was present in 35% of patients and was associated with increased 90 day all-cause mortality (unadjusted HR 9.16, 95% CI 1.98-42; P = 0.0046). Hazard ratio remained significant after adjusting for age, INTERMACS profile, serum creatinine, and total bilirubin. Findings were similar in the HM III subgroup. CONCLUSIONS: Hypotensive SBP response on pre-LVAD CPX is associated with increased perioperative and 90 day mortality after LVAD implantation. Additional studies are needed to determine the mechanism of increased mortality observed.

Right Ventricular Dysfunction is Associated with Increased Mortality in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019.

Respiratory failure caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is associated with mortality. Patients unresponsive to conventional therapy may benefit from temporary venovenous extracorporeal membrane oxygenation (VV-ECMO). We investigated clinical and echocardiographic characteristics, particularly, right ventricular dysfunction, with survival in patients with respiratory failure caused by SARS-CoV-2. We performed a single-center retrospective cohort study of patients requiring VV-ECMO for respiratory failure from COVID-19 infection between January 2020 and December 2020. Demographics, comorbidities, laboratory parameters, and echocardiographic features of left and right ventricular (LV/RV) function were compared between patients who survived and those who could not be weaned from VV-ECMO. In addition, we evaluated outcomes in a separate population managed with venoarterial extracorporeal membrane oxygenation (VA-ECMO). In total, 10/17 patients failed to wean from VV-ECMO and died in the hospital on average 41.5 ± 10.9 days post admission. Seven were decannulated (41%) and survived to hospital discharge. There were no significant differences in demographics, comorbidities, and laboratory parameters between groups. Moderate to severe RV dysfunction was significantly more in those who died (8/10, 80%) compared to survivors (0/7, 0%) (p = 0.002). Patients supported with VA-ECMO had superior survival with 5/9 patients (56%) decannulated and discharged. Moderate to severe RV dysfunction is associated with increased mortality in patients with respiratory failure requiring VV-ECMO for COVID-19.

COVID-19-Associated Myocarditis: An Evolving Concern in Cardiology and Beyond.

The direct and indirect adverse effects of SARS-CoV-2 infection on the cardiovascular system, including myocarditis, are of paramount importance. These not only affect the disease course but also determine clinical outcomes and recovery. In this review, the authors aimed at providing an update on the incidence of Coronavirus disease-2019 (COVID-19)-associated myocarditis. Our knowledge and experience relevant to this area continues to evolve rapidly since the beginning of the pandemic. It is crucial for the scientific and medical community to stay abreast of current information. Contrasting early reports, recent data suggest that the overall incidence of SARS-CoV-2-associated myocarditis is relatively low, yet infected individuals are at a substantially increased risk. Therefore, understanding the pathophysiology and diagnostic evaluation, including the use of serum biomarkers and imaging modalities, remain important. This review aims to summarize the most recent data in these areas as they relate to COVID-19-associated myocarditis. Given its increasing relevance, a brief update is included on the proposed mechanisms of myocarditis in COVID-19 vaccine recipients.

Fulminant myocarditis following coronavirus disease 2019 vaccination: a case report.

BACKGROUND: The BNT162b2 vaccine received emergency use authorization from the U.S. Food and Drug Administration for the prevention of severe coronavirus disease 2019 (COVID-19) infection. We report a case of biopsy and magnetic resonance imaging (MRI)-proven severe myocarditis that developed in a previously healthy individual within days of receiving the first dose of the BNT162b2 COVID-19 vaccine. CASE SUMMARY: An 80-year-old female with no significant cardiac history presented with cardiogenic shock and biopsy-proven fulminant myocarditis within 12 days of receiving the BNT162b2 COVID-19 vaccine. She required temporary mechanical circulatory support, inotropic agents, and high-dose steroids for stabilization and management. Ultimately, her cardiac function recovered, and she was discharged in stable condition after 2 weeks of hospitalization. A repeat cardiac MRI 3 months after her initial presentation demonstrated stable biventricular function and continued improvement in myocardial inflammation. DISCUSSION: Fulminant myocarditis is a rare complication of vaccination. Clinicians should stay vigilant to recognize this rare, but potentially deadly complication. Due to the high morbidity and mortality associated with COVID-19 infection, the clinical benefits of the BNT162b2 vaccine greatly outweighs the risks of complications.

Cardiac Transplantation and the Use of Cannabis.

Cardiac transplantation requires the careful allocation of a limited number of precious organs. Therefore, it is critical to select candidates that will receive the greatest anticipated medical benefit but will also serve as the best stewards of the organ. Individual transplant teams have established prerequisites pertaining to recreational drug, tobacco, alcohol, and controlled substance use in potential organ recipients and post-transplantation. Legalization of cannabis and implementation of its prescription-based use for the management of patients with chronic conditions have been increasing over the past years. Center requirements regarding abstinence from recreational and medical cannabis use vary due to rapidly changing state regulations, as well as the lack of clinical safety data in this population. This is evident by the results of the multicenter survey presented in this paper. Developing uniform guidelines around cannabis use will be imperative not only for providers but also for patients.

Computed Tomography Coronary Plaque Characteristics Predict Ischemia Detected by Invasive Fractional Flow Reserve.

PURPOSE: Coronary computed tomography angiography (CCTA) plaque quantification has been proposed to be of incremental value in the prediction of ischemia, although prior studies have shown conflicting results. We aimed to determine whether CCTA plaque features assessed on a commercial vendor platform predict invasive fractional flow reserve (FFR)/instantaneous wave-free ratio (IFR). METHODS: Consecutive patients who underwent CCTA for evaluation of suspected stable coronary artery disease followed by invasive coronary physiology testing within 60 days at a single academic center were identified retrospectively. Semiautomated plaque quantification of the vessel proximal to the location of FFR/IFR measurement was carried out in TeraRecon, along with simple visual assessment for high-risk plaque features of positive remodeling, spotty calcification, low-attenuation plaque (LAP), and lesion length. Ischemia was defined by FFR ≤0.80 or IFR ≤0.89. RESULTS: A total of 134 patients (62% male, mean age 62±10 y) were included in this study. On univariate logistic regression, the following visual plaque analysis parameters were predictive of ischemia: positive remodeling (odds ratio [OR] with 95% confidence interval [CI]: 4.96; 2.25-10.95; P<0.001), lesion length (OR for every 1 mm with 95% CI: 1.24; 1.14-1.34; P<0.001), spotty calcification (OR with 95% CI: 6.67; 1.67-26.64; P=0.007), and LAP (OR with 95% CI: 30; 3.78-246; P=0.001). None of the semiautomated plaque quantification parameters, such as noncalcified plaque volume or LAP volume, were predictive of ischemia. On stepwise multivariable logistic regression, lesion length (OR with 95% CI: 1.25; 1.14-1.37; P<0.0001) and LAP (OR with 95% CI: 43; 4.4-438; P=0.001) were significant predictors of ischemia, improving the area under the curve of CCTA from 0.53 to 0.87. CONCLUSIONS: Simple visual plaque assessment for high-risk plaque features improved the performance of CCTA to predict ischemia. Semiautomated plaque quantification performed on a commercial vendor platform was not predictive of ischemia.

Update on COVID-19 Myocarditis.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) gained worldwide attention at the end of 2019 when it was identified to cause severe respiratory distress syndrome. While it primarily affects the respiratory system, we now have evidence that it affects multiple organ systems in the human body. Cardiac manifestations may include myocarditis, life threatening arrhythmias, acute coronary syndrome, systolic heart failure, and cardiogenic shock. Myocarditis is increasingly recognized as a complication of Coronavirus-19 (COVID-19) and may result from direct viral injury or from exaggerated host immune response. The diagnosis is established similar to other etiologies, and is based on detailed history, clinical exam, laboratory findings and non-invasive imaging studies. When available, cardiac MRI is the preferred imaging modality. Endomyocardial biopsy may be performed if the diagnosis remains uncertain. Current management is mainly supportive with the potential addition of interventions recommended for severe COVID-19 disease, such as remdesivir, steroids, and convalescent plasma. In the setting of cardiogenic shock and refractory, life-threatening arrhythmias that persist despite medical therapy, advanced mechanical circulatory support devices should be considered. Ultimately, early recognition and aggressive intervention are key factors in reducing morbidity and mortality. Our management strategy is expected to evolve further as we learn more about COVID-19 disease and the associated cardiac complications.

Double Rule In: Concomitant Acute Coronary Occlusion and Pulmonary Embolism.

Computed tomography angiography is frequently used for double rule out of obstructive coronary artery disease and pulmonary embolism in patients presenting to the emergency department with acute chest pain, but it is rare to see concomitant acute coronary occlusion and pulmonary embolism on the same computed tomography angiography scan.

Drug-Induced Liver Injury in the Setting of Glycogenic Hepatopathy.

Glycogenic hepatopathy (GH) is an underdiagnosed complication of uncontrolled type 1 diabetes mellitus (T1DM). It appears as an acute relapsing hepatitis with reversible transaminase elevations secondary to excessive hepatic glycogen accumulation. Patients are often asymptomatic but can present with abdominal pain, nausea and vomiting. Physical examination shows hepatomegaly without splenomegaly. GH is diagnosed by biopsy as it is clinically indistinguishable from non-alcoholic fatty liver disease (NAFLD), a more common cause of hepatic dysfunction in diabetics. Here we describe a case of GH in a patient with uncontrolled type 1 diabetes whose clinical course was complicated by drug-induced liver injury. The patient initially presented with diabetic ketoacidosis and had a mild transaminitis, thought to be due to NAFLD. She developed profound transaminase elevations while receiving treatment with newer antipsychotic medications for her bipolar disorder. Liver biopsy showed evidence of resolving glycogenic hepatopathy with signs of drug-induced liver injury. This case report reviews the pathology and pathogenesis of GH and reminds the clinician to keep GH within the differential diagnosis for severe transaminitis in a patient with type 1 diabetes mellitus.