Survival After Simultaneous Heart-kidney Transplant in Recipients With a Durable LVAD and Chronic Kidney Disease: Effect of the 2018 Heart Allocation Policy Change.

BACKGROUND: Heart transplantation remains the most definitive therapy for qualified candidates with end-stage heart failure. Concomitant kidney disease is common in this population prompting an increase in simultaneous heart-kidney (SHK) transplantation in recent years. The goal of our study was to explore the effects of the 2018 heart allocation policy (HAP) change on candidate listing characteristics and compare survival rates at 1 y in patients that were supported with a left ventricular assist device (LVAD) pretransplant and underwent SHK or heart alone transplant (HAT). METHODS: We used data from the Scientific Registry of Transplant Recipients and identified all adults who underwent primary SHK or HAT between January 2010 and March 2022. Recipients supported with a durable LVAD and estimated glomerular filtration rate <60 mL/min/1.73 m 2 were selected (n = 309 SHK; 217 pre- and 92 post-HAP and n = 3,324 HAT; 2738 pre- and 586 post-HAP). RESULTS: Difference in survival at 1 y did not reach statistical significance. Comparing the 1-y survival of SHK and HAT recipients who were bridged with LVAD pre-HAP, we found no significant difference ( P = 0.694). Adjusting for the same covariates in a multivariable model did not affect the results (SHK versus HAT hazard ratio 0.84 [0.51, 1.37]; P = 0.48). In contrast, SHK recipients supported with an LVAD who were listed and transplanted post-HAP change had significantly lower 1-y survival, when compared with HAT ( P = 0.037). CONCLUSIONS: Our findings suggest that the HAP change had a potentially negative impact on the survival of select patients undergoing SHK transplant. Further research is warranted in this area.

Prognostic Role of Metabolic Exercise Testing in Heart Failure.

Heart failure is a clinical syndrome with significant heterogeneity in presentation and severity. Serial risk-stratification and prognostication can guide management decisions, particularly in advanced heart failure, when progression toward advanced therapies or end-of-life care is warranted. Each currently utilized prognostic marker carries its own set of challenges in acquisition, reproducibility, accuracy, and significance. Left ventricular ejection fraction is foundational for heart failure syndrome classification after clinical diagnosis and remains the primary parameter for inclusion in most clinical trials; however, it does not consistently correlate with symptoms and functional capacity, which are also independently prognostic in this patient population. Utilizing the left ventricular ejection fraction as the sole basis of prognostication provides an incomplete characterization of this condition and is prone to misguide medical decision-making when used in isolation. In this review article, we survey and exposit the important role of metabolic exercise testing across the heart failure spectrum, as a complementary diagnostic and prognostic modality. Metabolic exercise testing, also known as cardiopulmonary exercise testing, provides a comprehensive evaluation of the multisystem (i.e., neurological, respiratory, circulatory, and musculoskeletal) response to exercise performance. These differential responses can help identify the predominant contributors to exercise intolerance and exercise symptoms. Additionally, the aerobic exercise capacity (i.e., oxygen consumption during exercise) is directly correlated with overall life expectancy and prognosis in many disease states. Specifically in heart failure patients, metabolic exercise testing provides an accurate, objective, and reproducible assessment of the overall circulatory sufficiency and circulatory reserve during physical stress, being able to isolate the concurrent chronotropic and stroke volume responses for a reliable depiction of the circulatory flow rate in real time.

Genetic Evaluation and Screening in Cardiomyopathies: Opportunities and Challenges for Personalized Medicine.

Cardiomyopathy is a major cause of heart failure caused by abnormalities of the heart muscles that make it harder for it to fill or eject blood. With technological advances, it is important for patients and families to understand that there are potential monogenic etiologies of cardiomyopathy. A multidisciplinary approach to clinical genetic screening for cardiomyopathies involving genetic counseling and clinical genetic testing is beneficial for patients and families. With early identification of inherited cardiomyopathy, patients can initiate guideline-directed medical therapies earlier, resulting in a greater likelihood of improving prognoses and health outcomes. Identifying impactful genetic variants will also allow for cascade testing to determine at-risk family members through clinical (phenotype) screening and risk stratification. Addressing genetic variants of uncertain significance and causative variants that may change in pathogenicity is also important to consider. This review will dive into the clinical genetic testing approaches for the various cardiomyopathies, the significance of early detection and treatment, the value of family screening, the personalized treatment process associated with genetic evaluation, and current strategies for clinical genetic testing outreach.

Mortality associated with antiarrhythmic medication for atrial fibrillation among patients with left ventricular hypertrophy.

BACKGROUND: Atrial fibrillation (AF) guidelines recommend amiodarone as the preferred antiarrhythmic medication (AAM) in patients with left ventricular hypertrophy (LVH), due to potential pro-arrhythmic risk with other AAM. However, there are limited data to support this assertion. METHODS: We retrospectively analyzed the records of 8204 patients who were prescribed AAM for AF and had transthoracic echocardiogram (TTE) at the multicenter, VA Midwest Health Care Network from 2000 to 2021. We excluded patients without LVH (septal or posterior wall dimension ≤1.4 cm). The primary outcome variable was all-cause mortality during antiarrhythmic therapy or within 6 months after stopping it. Propensity-stratified analyses were performed between amiodarone versus non-amiodarone (Vaughan-Williams Class I and III) AAM. RESULTS: A total of 1277 patients with LVH (mean age 70.2 ± 9.5 years) were included in the analysis. Of these, 774 (60.6%) were prescribed amiodarone. Baseline characteristics of the two comparison groups were similar after propensity adjustment. After a median 1.40 years of follow-up, 203 (15.9%) patients died. Incidence rates per 100 patient-year follow-up was 9.02 (7.58-10.66) for amiodarone and 4.98 (3.91-62.56) for non-amiodarone. In propensity-stratified analysis, amiodarone use was associated with 1.58 times higher risk of mortality (95% CI 1.03-2.44; p = .038). Sub-group analysis in 336 (26.3%) patients with severe LVH showed no difference in mortality (HR 1.41, 95% CI 0.82-2.43, p = .21). CONCLUSION: Among patients with AF and LVH, amiodarone was associated with a significantly higher mortality risk than other AAM.

Supraglottic airway devices are associated with asphyxial physiology after prolonged CPR in patients with refractory Out-of-Hospital cardiac arrest presenting for extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Multiple randomized clinical trials have compared specific airway management strategies during ACLS with conflicting results. However, patients with refractory cardiac arrest died in almost all cases without the availability of extracorporeal cardiopulmonary resuscitation (ECPR). Our aim was to determine if endotracheal intubation (ETI) was associated with improved outcomes compared to supraglottic airways (SGA) in patients with refractory cardiac arrest presenting for ECPR. METHODS: We retrospectively studied 420 consecutive adult patients with refractory out-of-hospital cardiac arrest due to shockable presenting rhythms presenting to the University of Minnesota ECPR program. We compared outcomes between patients receiving ETI (n = 179) and SGA (n = 204). The primary outcome was the pre-cannulation arterial PaO2 upon arrival to the ECMO cannulation center. Secondary outcomes included neurologically favorable survival to hospital discharge and eligibility for VA-ECMO based upon resuscitation continuation criteria applied upon arrival to the ECMO cannulation center. RESULTS: Patients receiving ETI had significantly higher median PaO2 (71 vs. 58 mmHg, p = 0.001), lower median PaCO2 (55 vs. 75 mmHg, p < 0.001), and higher median pH (7.03 vs. 6.93, p < 0.001) compared to those receiving SGA. Patients receiving ETI were also significantly more likely to meet VA-ECMO eligibility criteria (85% vs. 74%, p = 0.008). Of patients eligible for VA-ECMO, patients receiving ETI had significantly higher neurologically favorable survival compared to SGA (42% vs. 29%, p = 0.02). CONCLUSIONS: ETI was associated with improved oxygenation and ventilation after prolonged CPR. This resulted in increased rate of candidacy for ECPR and increased neurologically favorable survival to discharge with ETI compared to SGA.

Agreement of Proximal Thoracic Aorta Size by Two-Dimensional Transthoracic Echocardiography and Magnetic Resonance Angiography.

There is currently a lack of uniformity in methods of aortic diameter measurements across different imaging modalities. In this study, we sought to evaluate the accuracy of transthoracic echocardiography (TTE) in comparison with magnetic resonance angiography (MRA) for the measurement of proximal thoracic aorta diameters. This is a retrospective analysis of 121 adult patients at our institution who had TTE and electrocardiogram  (ECG)-gated MRA performed within 90 days of each other between 2013 and 2020. Measurements were made at the level of sinuses of Valsalva (SoV), sinotubular junction (STJ), and ascending aorta (AA) using leading edge-to-leading edge (LE) convention for TTE and inner-edge-to-inner-edge (IE) convention for MRA. Agreement was assessed using Bland-Altman methods. Intra- and interobserver variability were assessed by intraclass correlation. The average age of patients in the cohort was 62 years, and 69% of patients were male. The prevalence of hypertension, obstructive coronary artery disease, and diabetes was 66%, 20%, and 11%, respectively. The mean aortic diameter by TTE was SoV 3.8 ± 0.5 cm, STJ 3.5 ± 0.4 cm, and AA 4.1 ± 0.6 cm. The TTE-derived measurements were larger than the MRA ones by 0.2 ± 2 mm, 0.8 ± 2 mm, and 0.4 ± 3 mm at the level of SoV, STJ, and AA, respectively, but the differences were not statistically significant. There were no significant differences in the aorta measurements by TTE compared with MRA, when stratified by gender. In conclusion, transthoracic echocardiogram-derived proximal aorta measurements are comparable to MRA measurements. Our study validates current recommendations that TTE is an acceptable modality for screening and serial imaging of the proximal aorta.

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.

A case of AL amyloidosis presenting with refractory ventricular fibrillation.

A 66-year-old male with recent diagnosis of heart failure with reduced ejection fraction was referred to our institution for management of cardiogenic/vasodilatory shock. During his evaluation, he suffered a sudden cardiac arrest from refractory ventricular tachycardia/fibrillation (VT/VF) despite normal electrolytes and no evidence of prior ventricular arrhythmias. He was placed on rescue peripheral veno-arterial extracorporeal membrane oxygenation support (VA-ECMO) for 4 days and was decannulated without end-organ damage. Continued workup revealed Mayo stage IV immunoglobulin light chain (AL) amyloidosis. Unfortunately, he developed acute cerebellar hemorrhage several days later. Autopsy findings were consistent with AL amyloidosis, with extensive cardiac fibrosis and amyloid deposition in the myocardium and vasculature. While the most common cause of cardiac death in patients with amyloidosis is severe bradycardia and pulseless electrical activity, sustained ventricular arrhythmias have been reported. The use of implantable cardioverter defibrillators (ICD) is highly debated in this population given the lack of survival benefit. Our patient also developed refractory VT/VF arrest, and ICD shocks would not have rescued him while causing significant distress. Emergent VA-ECMO cannulation allowed us to make a diagnosis, yet this intervention cannot be routinely recommended given the limited survival of patients with AL amyloidosis.

First Successful LVAD Implantation After BioVentrix Revivent TC Ventricular Reshaping.

The Revivent TC System (BioVentrix Inc, San Ramon, CA) enables a less invasive approach for left ventricular reshaping and scar exclusion in selected patients with ischemic cardiomyopathy. Although the system is designed to improve quality of life and to promote reverse remodeling, patients can still progress to end-stage heart failure requiring advanced therapies. This report describes a case of left ventricular assist device surgery in a patient 16 months after Revivent System implantation. The planning process and surgical technique proved to be complex. This case report can help provide guidance to advanced heart failure teams who encounter patients with the Revivent System who require left ventricular assist device support.

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.

Sex Differences in Takotsubo Syndrome: A Narrative Review.

Takotsubo syndrome (TTS), or apical ballooning syndrome, is a transient and usually reversible form of cardiac dysfunction. It has classically been described in women with cardiac susceptibility when exposed to emotional or physical stress. Various hypotheses on the pathophysiology of TTS have been suggested, but the underlying mechanism remains unknown. There is increasing recognition of the sex differences in the presentation, triggers, severity, and complications of TTS. A literature review was conducted and found 75 relevant articles on PubMed Cochrane Library, and Google Scholar from 2001 to 2019 regarding TTS. We found remarkable sex differences existed in the underlying triggers, pathophysiology, illness severity, complications, and mortality. However, no sex differences were identified for baseline transthoracic echocardiogram findings, age at presentation, presenting symptoms, recurrence, and treatment approach. Much information regarding TTS remain lacking, but collaboration of national and international registries will be beneficial in addressing these gaps.

Patent foramen ovale and ascending aortic aneurysm causing the platypnea-orthodeoxia syndrome.

Patent foramen ovale (PFO) is present in about 25% of the population. Platypnea-orthodeoxia syndrome (POS), which is dyspnea and hypoxemia in the upright position that is relieved when supine, is a rare manifestation of PFO. We describe a case of a 74-year-old woman who presented with new-onset hypoxia. A PFO and a dilated aorta causing POS were found on workup. Symptoms were resolved after undergoing percutaneous PFO closure. This case highlights the mechanism by which an ascending aortic aneurysm can alter hemodynamics through an existing PFO, leading to symptoms of a previously clinically insignificant PFO, and emphasizes how early recognition of POS allows for appropriate intervention.