Outcomes in patients with aortic stenosis and severely reduced ejection fraction following surgical aortic valve replacement and transcatheter aortic valve replacement.

BACKGROUND: Patients with severe aortic stenosis (AS) and left ventricular (LV) dysfunction demonstrate improvement in left ventricular injection fraction (LVEF) after aortic valve replacement (AVR). The timing and magnitude of recovery in patients with very low LVEF (≤ 25%) in surgical or transcatheter AVR is not well studied. OBJECTIVE: Determine clinical outcomes following transcatheter aortic valve replacement (TAVR) and surgical aortic valve repair (SAVR) in the subset of patients with severely reduced EF ≤ 25%. METHODS: Single-center, retrospective study with primary endpoint of LVEF 1-week following either procedure. Secondary outcomes included 30-day mortality and delayed postprocedural LVEF. T-test was used to compare variables and linear regression was used to adjust differences among baseline variables. RESULTS: 83 patients were enrolled (TAVR = 56 and SAVR = 27). TAVR patients were older at the time of procedure (TAVR 77.29 ± 8.69 vs. SAVR 65.41 ± 10.05, p < 0.001). One week post procedure, all patients had improved LVEF after both procedures (p < 0.001). There was no significant difference in LVEF between either group (TAVR 33.5 ± 11.77 vs. SAVR 35.3 ± 13.57, p = 0.60). Average LVEF continued to rise and increased by 101% at final follow-up (41.26 ± 13.70). 30-day mortality rates in SAVR and TAVR were similar (7.4% vs. 7.1%, p = 0.91). CONCLUSION: Patients with severe AS and LVEF ≤ 25% have a significant recovery in post-procedural EF following AVR regardless of method. LVEF doubled at two years post-procedure. There was no significant difference in 30-day mortality or mean EF recovery between TAVR and SAVR. TRIAL REGISTRATION: Indiana University institutional review board granted approval for above study numbered 15,322.

Sex Differences in Circulating Biomarkers of Heart Failure.

PURPOSE OF REVSIEW: Evidence is scaling up for sex differences in heart failure; however, clinical relevance of sex-specific differential thresholds for biomarkers is not clearly known. Current ambiguity warrants a further look into the sex-specific studies on cardiac biomarkers and may facilitate understanding of phenotypic presentations, clinical manifestations, and pathophysiologic pathway differences in men and women. RECENT FINDINGS: Recent studies have confirmed the fact that females have differential threshold for biomarkers, with lower troponin and higher NT proBNP levels. Ambiguity continues to exist in the clinical relevance of ST-2, Galectin 3, and other biomarkers. Novel biomarkers, proteomic biomarkers, and circulating micro RNAs with machine learning are actively being explored. Biomarkers in HFpEF patients with higher female representation are evolving. In recent clinical trials, sex-related difference in biomarkers is not seen despite therapeutic intervention being more effective in females compared to males. Sex-related difference exists in the expression of biomarkers in health and in various disease states of heart failure. However, this differentiation has not effectively translated into the clinical practice in terms of diagnostic studies or prognostication. Active exploration to bridge the knowledge gap and novel technologies can shed more light in this area.

No Evidence for Oversizing Hearts and Donor Size Impact on 1-Year Survival in Heart Failure Patients With Left Ventricular Assist Device.

The predicted heart mass (PHM) ratio has recently emerged as a better metric for donor-to-recipient size-matching than weight ratios. It is unknown whether this applies to transplant candidates on left ventricular assist device (LVAD) support. Our study examines if PHM ratio is optimal for size-matching specifically in the LVAD patient population. Patients with LVAD who received a heart transplant from January 1997 to December 2020 in the Scientific Registry of Transplant Recipients database were studied. We compared 5 size-matching metrics, including donor-recipient ratios of weight, height, body mass index, body surface area, and PHM. Single and multivariable Cox proportional hazards models for 1-year mortality were calculated. Our sample consisted of 11,891 patients. In our multivariate analysis, we found that patients in the undersized group with PHM ratios <0.83 had a hazard ratio for 1-year mortality of 1.34 (95% confidence interval 1.08 to 1.65, p = 0.007) suggestive of increased mortality with the use of undersized donors. There was no statistical difference in mortality between the matched (PHM ratio 0.83 to 1.2) and oversized group (PHM ratio ≥1.2). In heart transplant recipients on LVAD support, the PHM ratio provides better risk stratification than other metrics. Use of undersized donor hearts with PHM ratio <0.83 confers higher 1-year mortality. Using oversized donor hearts for transplantation in recipients on LVAD support has no benefit.

Using Sacubitril/Valsartan to Decrease Health care Costs in Population Health Patients.

Value-based care is the foundation of population health. The Health care Economic Efficiency Ratio (HEERO) scoring system is a promising new tool to measure the cost benefits of care in our Accountable Care Organization. HEERO score compares actual costs spent (utilizing insurance claims) and expected costs spent (estimated using the Centers for Medicare/Medicaid Services Risk score). Scores <1 suggest economic benefit. Sacubitril/valsartan has been shown to decrease readmissions for patients with heart failure (HF) and decrease health care costs. We explored the utility of sacubitril/valsartan in reducing HEERO scores and decreasing overall health care expenditure in patients with HF. Patients with HF in the population health cohort were enrolled. HEERO score was calculated for patients taking sacubitril/valsartan and other HF medications at 3-month intervals up to a year. We compared the average and total health care expenditure and inpatient days for patients on sacubitril/valsartan, spironolactone, ß blocker (BB) along with spironolactone, BB and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. For patients on sacubitril/valsartan, HEERO scores and inpatient days decreased (decreased health care expenditure) as the number of days of utilization increased (p <0.0001). In total, 270+ days of sacubitril/valsartan decreased health care costs by 22%. This cost reduction was mainly attributed to decreased inpatient days. Additionally, the combination of sacubitril/valsartan, spironolactone, and BB showed decreased HEERO score and inpatient days compared with spironolactone, BB and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in male patients. Sacubitril/valsartan use beyond 270 days resulted in decreased health care expenditure in a population health cohort compared with other HF medications. This economic benefit is achieved through the reduction in hospitalizations. Sacubitril/valsartan is an integral part of value-based care providing high-value, cost-effective care, and bolstering the economic wellbeing of patient care. Payor sources should consider this in subsidizing the cost of the medicine.

Aortic Thrombosis in Patients on Mechanical Circulatory Support: A Systematic Literature Review.

BACKGROUND: Aortic valve (AV) thrombosis is an uncommon but ominous complication in patients managed with mechanical circulatory support (MCS) devices. In this systematic review, we summarised the data on clinical presentations and outcomes in such patients. METHODS: We searched articles on PubMed and Google Scholar, reporting at least one adult patient with aortic thrombosis on MCS support and where the individual patient data could be extracted. We grouped the patients by the type of MCS (temporary or durable), and the type of the AV (prosthetic, surgically modified, or native) RESULTS: We identified reports on six patients with aortic thrombus on short-term MCS, and on 41 patients on durable left ventricular assist devices (LVADs). On temporary MCS, AV thrombus typically causes no symptoms and is found incidentally pre- or intra-operatively. For those with durable MCS, the occurrence of aortic thrombus forming on prosthetic or surgically modified valves appears to be more related to the intervention on the valve, rather than from the presence of LVAD. The mortality in this group was 18%. In patients with native AV on durable LVAD support, 60% of patients presented with acute myocardial infarction, acute stroke, or acute heart failure, and mortality in this cohort was 45%. In terms of management, heart transplantation was most successful. CONCLUSIONS: While the outcomes of aortic thrombosis were good in patients where temporary MCS was used in the setting of aortic valve surgery, patients with native AV who develop this complication on durable LVAD have high morbidity and mortality. Cardiac transplantation should be strongly considered in eligible candidates because other therapies provide inconsistent results.

PCSK9 Inhibition in Patients After Heart Transplantation: a Retrospective Review and Literature Analysis.

PURPOSE OF REVIEW: Following cardiac transplantation, patients have an increased risk of developing cardiac allograft vasculopathy and atherosclerotic cardiovascular disease. Therefore, aggressive lipid management is indicated. Some patients do not achieve optimal lipid profiles with statin monotherapy, however, or discontinue statins due to intolerance. In this review, we investigated the use of PCSK9 inhibitors as an alternative treatment for hyperlipidemia following cardiac transplantation. RECENT FINDINGS: Nine published articles were identified that included 110 patients treated with alirocumab or evolocumab after cardiac transplantation. PCSK9 inhibitors were tolerated by all patients, and each study demonstrated an effective reduction of low-density lipoprotein ranging from 40 to 87% decrease from baseline. In our study, the 110 patients from literature review were added to a cohort of 7 similar patients from our institution for combined analysis. This report supports that PCSK9 inhibitors should be considered following cardiac transplantation when conventional medial therapy is not tolerated or ineffective.

Donor substance abuse and heart transplantation outcomes.

Heart failure continues to account for millions of cases and deaths worldwide. Heart transplant is the gold standard for treatment of advanced heart failure. Unfortunately, the supply of donor hearts continues to be limited with the increase in demand for heart transplantation. In this review, we aim to explore the safety and efficacy of using hearts from donors with history of substance use. Despite the theoretical effect of cocaine and alcohol on the cardiovascular system, several studies demonstrate no difference in outcomes (overall survival, graft rejection, graft vasculopathy) when using hearts from patients with history of cocaine and alcohol use. The opioid epidemic has expanded the potential donor pool where the current studies have not shown any adverse outcomes when considering donors with history of opioid use. The currently available evidence would support the use of donor hearts from patients with history of alcohol, cocaine, opioids, and marijuana use. Further studies are needed to evaluate the safety of using donor hearts from patients with history of nicotine use.

Special Considerations in the Care of Women With Advanced Heart Failure.

Advanced heart failure (AHF) is associated with increased morbidity and mortality, and greater healthcare utilization. Recognition requires a thorough clinical assessment and appropriate risk stratification. There are persisting inequities in the allocation of AHF therapies. Women are less likely to be referred for evaluation of candidacy for heart transplantation or left ventricular assist device despite facing a higher risk of AHF-related mortality. Sex-specific risk factors influence progression to advanced disease and should be considered when evaluating women for advanced therapies. The purpose of this review is to discuss the role of sex hormones on the pathophysiology of AHF, describe the clinical presentation, diagnostic evaluation and definitive therapies of AHF in women with special attention to pregnancy, lactation, contraception and menopause. Future studies are needed to address areas of equipoise in the care of women with AHF.

Don't Break My Heart: A Case Report of Takotsubo Syndrome in a Transplanted Heart.

Cardiogenic shock after heart transplant, could be due to acute rejection, cardiac allograft vasculopathy, or myocarditis. Stress cardiomyopathy (CM) in a denervated transplanted heart is unusual. A 56-year-old man with a history of ischemic heart disease and a seizure disorder underwent orthotropic heart transplant. He had breakthrough seizures posttransplant while on levetiracetam (Keppra) and was admitted for status epilepticus. A transthoracic echocardiogram (TTE) was done for hypotension (BP 90/60). TTE showed a severely reduced left ventricular ejection fraction (LVEF) of 15%, hyperkinetic base, and apical ballooning that are consistent with stress CM. Electrocardiogram with T wave inversion in precordial leads. Troponin was elevated to 1.77. The patient had cardiogenic shock and needed an intra-aortic balloon pump and multiple pressors. He was treated for status epilepticus and the LVEF completely recovered in 1 week. The patient had a normal TTE, coronary angiography, and biopsy with no rejection 8 days before admission. Stress CM was the diagnosis of exclusion, confirmed with a complete recovery of the LVEF. There are only 5 case reports of stress CM after heart transplant, with most presenting 9 to 10 years afterwards. We describe an unusual case of cardiogenic shock from stress CM triggered by status epilepticus in a denervated heart only 1 year posttransplant. The mechanism is elusive, and some hypotheses suggest exaggerated sensitivity to a plasma catecholamine surge from parasympathetic denervation. In a denervated heart, autonomic re-innervation can be seen as early as 1 year posttransplant.

Comparison of and Frequency of Mortality, Left Ventricular Assist Device Implantation, Ventricular Arrhythmias, and Heart Transplantation in Patients With Familial Versus Nonfamilial Idiopathic Dilated Cardiomyopathy.

We postulated that familial idiopathic dilated cardiomyopathy (F-IDC) is associated with a worse prognosis than nonfamilial IDC (nonF-IDC). Patients with F-IDC had either a strong family history and/or proved genetic mutations. We studied long-term prognosis (mean follow-up: 6.1 ± 4.1 years) of 162 patients with IDC (age: 55.5 ± 17.9 years, men: 57.8%, 50% F-IDC) with an implantable cardioverter-defibrillator or cardiac resynchronization therapy. The primary end point was a composite of death, left ventricular (LV) assist device implant, or heart transplantation. The secondary end point was a ventricular arrhythmia event. There was no significant difference in the prevalence of diabetes, hypertension, New York Heart Association class, medical therapy, and years of follow-up between the F-IDC and nonF-IDC groups. Patients with F-IDC were younger than patients with nonF-IDC (49.1 ± 17.0 years vs 61.6 ± 16.5 years, p <0.001). Mean LV ejection fraction was significantly lower in F-IDC group than in the nonF-IDC group (26 ± 12% vs 31 ± 12%, p = 0.022). The primary end point was achieved in 54 patients in F-IDC group (66.7%) versus 19 in the nonF-IDC group (23.5%) (p <0.001). The Kaplan-Meier survival estimates for the composite end point and for ventricular arrhythmia were significantly lower in the F-IDC versus nonF-IDC (log-rank p ≤0.001 and 0.04, respectively). F-IDC was the only multivariable predictor of the primary composite end point (hazard ratio 3.419 [95% confidence interval 1.845 to 6.334], p <0.001). The likelihood of LV remodeling manifested by LV ejection fraction improvement (≥10%) was significantly lower in F-IDC than nonF-IDC (27.1% vs 44.8%, p = 0.042). In conclusion, F-IDC is a predictor of mortality, need for LV assist device, or heart transplantation. F-IDC is associated with significantly lower event-free survival for primary end point and ventricular arrhythmia than nonF-IDC. F-IDC has significantly lower likelihood of LV reverse remodeling than nonF-IDC.

Subjective and Objective Impact of Angiotensin Receptor-Neprilysin Inhibitors on Systemic Right Ventricle Patients.

INTRODUCTION: Patients with adult congenital heart disease (ACHD) who have an anatomic right ventricle supporting the systemic circulation have increased mortality and morbidity from heart failure (HF). Angiotensin receptor-neprilysin inhibitors (ARNI) have emerged as a standard of therapy for adults with HF. However, the effects of this therapy have not been extensively studied in ACHD patients, especially those with systemic right ventricle (SRV). HYPOTHESIS: ARNIs are associated with subjective and objective improvement in SRV patients. METHODS: Eighteen (18) SRV patients were prescribed ARNI at our institution in the last 5 years. Data before and during treatment, including demographics, medical history, New York Heart Association functional class (NYHA FC), labs, cardiac computed tomography (CT) or magnetic resonance imaging (MRI), echocardiographic measurements, cardiopulmonary stress test (CPET), and hospitalisation for HF were obtained by review of the electronic medical record. Statistical analysis was performed using paired t and Wilcoxon rank sum tests. RESULTS: Eighteen (18) SRV patients (mean age 40 yrs, 72% male) were treated with ARNI (median duration 13 mo) in addition to other HF medications. All patients tolerated ARNI without symptomatic or asymptomatic hypotension or worsening kidney function. High ARNI dose (97/103 mg) was achieved in three (17%) patients, and moderate (49/51 mg) in three (17%). At baseline, nine patients were NYHA FC 2, seven FC 3, and two FC 4. Mean baseline cardiopulmonary exercise testing (CPET) and echocardiographic data were: oxygen uptake (VO2) 18 mL/kg/min, minute ventilation/carbon dioxide (VE/VCO2) 38, right ventricular ejection fraction (RVEF) 32%, fractional area change (FAC) 21%. Significant tricuspid regurgitation was present in 33% (28% moderate, and 5% severe) and mean tricuspid annular plane systolic excursion (TAPSE) was 9.4 mm. With treatment, there was no statistically significant difference in blood pressure, labs, testing, or imaging. There was a statistically significant improvement in median NYHA FC (2 vs 2.5, p=0.005). When compared to an equal pre-ARNI median timeframe, there was a noted decrease in cardiac hospitalisation (4 vs 9) that did not reach statistical significance (p=0.313). CONCLUSION: In adult patients with failing systemic right ventricle, ARNI is safe and well tolerated. Their use is associated with improvement in functional status. Prospective studies on a larger group of patients are warranted to better understand the causes of this improvement.

Heart transplantation in systemic lupus erythematosus: A case report and meta-analysis.

Cardiac involvement in Systemic Lupus Erythematosus can present as end stage heart failure necessitating orthotopic heart transplantation. Most transplant centers regard Lupus as a contraindication to transplant due to risk of disease recurrence in the transplanted organ. Limited reports of heart transplant in Lupus exist in the literature. Herein, we aim to report on the successful transplant and long-term survival of a 24-year-old woman with Lupus and biventricular heart failure. Given the rarity of transplant in Lupus, we also conducted a meta-analysis of reported cases in the literature to assess post-transplant outcomes and evaluate immunosuppression strategies. Our case underlines the feasibility of transplant in Lupus patients, outlines a detailed immunosuppression strategy and favorable long-term outcome to guide centers contemplating such transplants. The long-term survival of our patient, together with review of the thirteen previously described cases, supports that orthotopic heart transplantation can be considered in select patients with Systemic Lupus Erythematosus.

Heart Transplantation in Mustard Patients Bridged With Continuous Flow Systemic Ventricular Assist Device - A Case Report and Review of Literature.

Thirty four-year-old male with history of D-transposition of the great arteries (D-TGA) who underwent Mustard operation at 14 months of age presented in cardiogenic shock secondary to severe systemic right ventricular failure. Catheterization revealed significantly increased pulmonary pressures. Due to the patient's inotrope dependence and prohibitive pulmonary hypertension, he underwent implantation of a Heart Ware HVAD® for systemic RV support. Within 4 months of continuous flow ventricular assist device (VAD) implantation complete normalization of pulmonary vascular resistance (PVR) was achieved. He ultimately underwent orthotopic heart transplantation with favorable outcomes. This is the second report of complete normalization of PVR following VAD implantation into a systemic RV in <4 months. We conducted a thorough literature review to identify Mustard patients that received systemic RV VAD as a bridge to a successful heart transplantation. In this article, we summarize the outcomes and focus on pulmonary hypertension reversibility following VAD implant.

Safety and feasibility of dopamine-atropine stress echocardiography.

BACKGROUND: Dobutamine-atropine stress echocardiography (DSE) has lower sensitivity in patients with advanced liver disease (ALD) due to vasodilation. HYPOTHESIS: Dopamine-atropine stress echocardiography (DopSE) may be an alternative to DSE in ALD patients by improving the blood pressure response to stress. METHODS: The safety and tolerability of DSE and DopSE were compared in 10 volunteers. The safety, adverse effects, and efficacy of DopSE were then assessed in 105 patients, 98 of whom had ALD. Dopamine was infused in stepwise fashion from 5 µg/kg/min to a peak dose of 40 µg/kg/min. Atropine was given before and in early stages of dopamine infusion up to cumulative dose of 1.5 mg. The hemodynamic responses of 98 ALD patients were compared with 102 patients with ALD who underwent standard DSE. RESULTS: In normal volunteers, systolic BP increased more with DopSE compared to DSE (61 ± 19 mm Hg vs 39 ± 15 mm Hg, P = .008). In 105 patients who underwent DopSE, none had adverse effects that required early stress termination. In the groups with ALD, the systolic BP increase (38 ± 28 mm Hg vs 12 ± 27 mm Hg, P < .001) and peak rate pressure product (RPP) (22 861 ± 5289 vs 17 211 ± 3848, P = <.001) were both higher in those undergoing DopSE versus DSE. The sensitivity and specificity of DopSE were 45% and 88%, respectively for coronary disease (≥70% stenosis) in 37 patients who had angiography. CONCLUSIONS: Dopamine-atropine stress echocardiography appears to be a safe stress modality and provides greater increases in RPP in patients with ALD compared to DSE.

Fulminant myocarditis: COVID or not COVID? Reinfection or co-infection?

We describe a unique case of fulminant myocarditis in a patient with presumed SARS-CoV-2 reinfection. Patient had initial infection 4 months backand had COVID-19 antibody at the time of presentation. Endomyocardial biopsy showed lymphocytic myocarditis, that is usually seen in viral myocarditis. The molecular diagnostic testing of the endomyocardial biopsy for cardiotropic viruses was positive for Parvovirus and negative for SARS-CoV-2. Authors highly suspect co-infection of SARS-CoV-2 and Parvovirus, that possibly triggered the immune cascade resulting in fulminant myocarditis. Patient was hemodynamically unstable with ventricular tachycardia and was supported on VA ECMO and Impella CP. There was impressive recovery of left ventricular function within 48 h, leading to decannulation of VA ECMO in 72 h. This unique case was written by the survivor herself.

Ambulatory advanced heart failure patients: timing of mechanical circulatory support - delaying the inevitable?

PURPOSE OF REVIEW: Current indications for continuous-flow left ventricular assist device (cfLVAD) implantation is for patients in cardiogenic shock or inotrope-dependent advanced heart failure. Risk stratification of noninotrope dependent ambulatory advanced heart failure patients is a subject of registries designed to help shared-decision making by clinicians and patients regarding the optimal timing of mechanical circulatory support (MCS). RECENT FINDINGS: The Registry Evaluation of Vital Information for VADs in Ambulatory Life enrolled ambulatory noninotrope dependent advanced systolic heart failure patients who had 25% annualized risk of death, MCS, or heart transplantation (HT). Freedom from composite clinical outcome at 1-year follow-up was 23.5% for the entire cohort. Seattle Heart Failure Model Score and Natriuretic pepides were predictors with modest discriminatory power. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 4 patients had the highest risk (3.7-fold) of death, MCS or HT compared to INTERMACS profile 7. SUMMARY: We propose individualized risk stratification for noninotrope dependent ambulatory advanced heart failure patients and include serial changes in end-organ function, nutritional parameters, frailty assessment, echocardiographic and hemodynamic data. The clinical journey of a patient with advanced heart failure should be tracked and discussed at each clinic visit for shared decision-making regarding timing of cfLVAD.

When to Use Cardiovascular Magnetic Resonance in Patients with Heart Failure.

Use of cardiac magnetic resonance (CMR) to aid in diagnosis, management, and prognosis of ischemic and nonischemic cardiomyopathy has advanced tremendously in the past several decades. These advances have expanded our understanding of both ischemic and nonischemic cardiomyopathies while also allowing for new avenues of diagnosis and treatment. This review summarizes key concepts of CMR technology and CMR use in the diagnosis and prognosis in ischemic, infiltrative, inflammatory, and other nonischemic cardiomyopathies and discusses the use of CMR in the patient presenting with ventricular arrhythmia with unclear diagnosis and advances in CMR in the management cardiomyopathy.

A Unique Case of Systemic Lupus Erythematosus Myocarditis Complicated by Plasmapheresis-Responsive Cardiogenic Shock.

A 25-year-old woman with systemic lupus erythematosus complicated by biventricular failure with a history of multiple admissions presented with cardiogenic shock unresponsive to steroids, intravenous immunoglobulin, cyclophosphamide, and required extra-corporeal membrane oxygenation. Left ventricular function eventually recovered after plasmapheresis. (Level of Difficulty: Advanced.).