Management of Iron Deficiency in Heart Failure: Practical Considerations and Implementation of Evidence-Based Iron Supplementation.

Iron deficiency (ID) is present in approximately 50% of patients with heart failure (HF) and even higher prevalence rate up to 80% in post-acute HF setting. The current guidelines for HF recommend intravenous (IV) iron replacement in HF with reduced or mildly reduced ejection fraction and ID based on clinical trials showing improvements in quality of life and exercise capacity, and an overall treatment benefit for recurrent HF hospitalization. However, several barriers cause challenges in implementing IV iron supplementation in practice due, in part, to clinician knowledge gaps and limited resource availability to protocolize routine utilization in appropriate patients. Thus, the current review will discuss practical considerations in ID treatment, implementation of evidence-based ID treatment to improve regional health disparities with toolkits, inclusion/exclusion criteria of IV iron supplementation, and clinical controversies in ID treatment, as well as gaps in evidence and questions to be answered.

Clinical outcomes among cardiogenic shock patients supported with high-capacity Impella axial flow pumps: A report from the Cardiogenic Shock Working Group.

BACKGROUND: The Impella 5.0 and 5.5 pumps (Abiomed, Danvers, MA) are large-bore transvalvular micro-axial assist devices used in cardiogenic shock (CS) for patients requiring high-capacity flow. Despite their increasing use, real-world data regarding indications, rates of utilization and clinical outcomes with this therapy are limited. The objective of our study was to examine clinical profiles and outcomes of patients in a contemporary, real-world CS registry of patients who received an Impella 5.0/5.5 alone or in combination with other temporary mechanical circulatory support (tMCS) devices. METHODS: The CS Working Group (CSWG) Registry includes patients from 34 US hospitals. For this analysis, data from patients who received an Impella 5.0/5.5 between 2020-2023 were analyzed. Use of Impella 5.0/5.5 with or without additional tMCS therapies, duration of support, adverse events and outcomes at hospital discharge were studied. Adverse events including stroke, limb ischemia, bleeding and hemolysis were not standardized by the registry but reported per individual CSWG Primary Investigator discretion. For those who survived, rates of native heart recovery (NHR) or heart replacement therapy (HRT) including heart transplant (HT), or durable ventricular assist device (VAD) were recorded. We also assessed outcomes based on shock etiology (acute myocardial infarction or MI-CS vs. heart failure-related CS or HF-CS). RESULTS: Among 6,205 patients, 754 received an Impella 5.0/5.5 (12.1%), including 210 MI-CS (27.8%) and 484 HF-CS (64.1%) patients. Impella 5.0/5.5 was used as the sole tMCS device in 32% of patients, while 68% of patients received a combination of tMCS devices. Impella cannulation sites were available for 524/754 (69.4%) of patients, with 93.5% axillary configuration. Survival to hospital discharge for those supported with an Impella 5.0/5.5 was 67%, with 20.4% NHR and 45.5% HRT. Compared to HF-CS, patients with MI-CS supported on Impella 5.0/5.5 had higher in-hospital mortality (45.2% vs 26.2%, p < 0.001) and were less likely to receive HRT (22.4% vs 56.6%, p < 0.001. For patients receiving a combination of tMCS during hospitalization, this was associated with higher rates of limb ischemia (9% vs. 3%, p < 0.01), bleeding (52% vs 33%, p < 0.01), and mortality (38% vs 25%; p < 0.001) compared to Impella 5.0/5.5 alone. Among Impella 5.0/5.5 recipients, the median duration of pump support was 12.9 days (IQR: 6.8-22.9) and longer in patients bridged to HRT (14 days; IQR: 7.7-28.4). CONCLUSIONS: In this multi-center cohort of patients with CS, use of Impella 5.0/5.5 was associated with an overall survival of 67.1% and high rates of HRT. Lower adverse event rates were observed when Impella 5.0/5.5 was the sole support device used. Further study is required to determine whether a strategy of early Impella 5.0/5.5 use for CS improves survival. CONDENSED ABSTRACT: High capacity Impella heart pumps are capable of provide up to 5.5 liter/min of flow while upper body surgical placement allows for ambulation. Patients with advanced cardiogenic shock from acute myocardial infarction or heart failure requiring temporary mechanical circulatory support may benefit from upfront use of Impella 5.5 to improve overall survival, including native heart recovery or successful bridge to durable left ventricular assist device surgery or heart transplantation.

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.

Multicenter registry and test bed for extended outpatient hemodynamic monitoring: the hemodynamic frontiers in heart failure (HF2) initiative.

Background: Hemodynamic Frontiers in Heart Failure (HF2) is a multicenter academic research consortium comprised of 14 US institutions with mature remote monitoring programs for ambulatory patients with heart failure (HF). The consortium developed a retrospective and prospective registry of patients implanted with a wireless pulmonary artery pressure (PAP) sensor. Goals/aims: HF2 registry collects demographic, clinical, laboratory, echocardiographic (ECHO), and hemodynamic data from patients with PAP sensors. The aims of HF2 are to advance understanding of HF and to accelerate development of novel diagnostic and therapeutic innovations. Methods: HF2 includes adult patients implanted with a PAP sensor as per FDA indications (New York Heart Association (NYHA) Class III HF functional class with a prior hospitalization, or patients with NYHA Class II or brain natriuretic peptide (BNP) elevation without hospitalization) at a HF2 member site between 1/1/19 to present. HF2 registry is maintained at University of Kansas Medical Center (KUMC). The registry was approved by the institutional review board (IRB) at all participating institutions with required data use agreements. Institutions report data into the electronic registry database using REDCap, housed at KUMC. Results: This initial data set includes 254 patients implanted from the start of 2019 until May 2023. At time of device implant, the cohort average age is 73 years old, 59.8% are male, 72% have NYHA Class III HF, 40% have left ventricular ejection fraction (LVEF) < 40%, 35% have LVEF > 50%, mean BNP is 560 pg/ml, mean N-Terminal pro-BNP (NTproBNP) is 5,490 pg/ml, mean creatinine is 1.65 mg/dl. Average baseline hemodynamics at device implant are right atrial pressure (RAP) of 11 mmHg, pulmonary artery systolic pressure (PASP) of 47 mmHg, pulmonary artery diastolic pressure (PADP) 21 mmHg, mean pulmonary artery pressure (mPAP) of 20 mmHg, pulmonary capillary wedge pressure (PCWP) of 19 mmHg, cardiac output (CO) of 5.3 L/min, and cardiac index (CI) of 2.5 L/min/m2. Conclusion: A real-world registry of patients implanted with a PAP sensor enables long-term evaluation of hemodynamic and clinic outcomes in highly-phenotyped ambulatory HF patients, and creates a unique opportunity to validate and test novel diagnostic and therapeutic approaches to HF.

A case report of constrictive pericarditis following COVID-19 vaccination.

Background: COVID-19 infection and the COVID-19 vaccines have been associated with rare cases of pericarditis. We present a case of constrictive pericarditis (CP) following the vaccine. Case summary: A 19-year-old healthy male started having progressive abdominal pain, emesis, dyspnoea, and pleuritic chest pain 2 weeks after the second dose of Pfizer vaccine. Computed tomography angiography chest revealed bilateral pleural effusions and pericardial thickening with effusion. Cardiac catheterization showed ventricular interdependence. Cardiac magnetic resonance (CMR) showed septal bounce and left ventricular tethering suggestive of CP. A total pericardiectomy was performed with significant symptom improvement. Pathology showed chronic fibrosis without amyloid, iron deposits, or opportunistic infections. Patient had Epstein-Barr Virus (EBV) viraemia 825 IU/mL and histoplasmosis complement-fixation positive with negative serum and urine antigen. Hypercoagulable panel and infectious workup were otherwise negative. The patient had resolution of cardiac symptoms at 3 months of follow-up. Discussion: The patient developed progressive symptoms within 2 weeks of his second Pfizer vaccine. Echocardiogram and CMR had classic signs of CP, and pericardial pathology confirmed fibrotic pericardium. The patient had no prior surgery, thoracic radiation, or bacterial infection. Epstein-Barr Virus viraemia was thought to be reactionary, and histoplasmosis complement likely represented chronic exposure. The timing of symptoms and negative multidisciplinary workup raises the suspicion for COVID vaccine-induced CP. The COVID vaccines benefits far exceed the risks, but complications still can occur. Practitioners should have a high index of suspicion to allow prompt diagnosis of CP.

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.

Fulminant Myocarditis and Cardiogenic Shock Following COVID-19 Infection Versus COVID-19 Vaccination: A Systematic Literature Review.

BACKGROUND: Myocarditis, diagnosed by symptoms and troponin elevation, has been well-described with COVID-19 infection, as well as shortly after COVID-19 vaccination. The literature has characterized the outcomes of myocarditis following COVID-19 infection and vaccination, but clinicopathologic, hemodynamic, and pathologic features following fulminant myocarditis have not been well-characterized. We aimed to compare clinical and pathological features of fulminant myocarditis requiring hemodynamic support with vasopressors/inotropes and mechanical circulatory support (MCS), in these two conditions. METHODS: We analyzed the literature on fulminant myocarditis and cardiogenic shock associated with COVID-19 and COVID-19 vaccination and systematically reviewed all cases and case series where individual patient data were presented. We searched PubMed, EMBASE, and Google Scholar for "COVID", "COVID-19", and "coronavirus" in combination with "vaccine", "fulminant myocarditis", "acute heart failure", and "cardiogenic shock". The Student's t-test was used for continuous variables and the χ2 statistic was used for categorical variables. For non-normal data distributions, the Wilcoxon Rank Sum Test was used for statistical comparisons. RESULTS: We identified 73 cases and 27 cases of fulminant myocarditis associated with COVID-19 infection (COVID-19 FM) and COVID-19 vaccination (COVID-19 vaccine FM), respectively. Fever, shortness of breath, and chest pain were common presentations, but shortness of breath and pulmonary infiltrates were more often present in COVID-19 FM. Tachycardia, hypotension, leukocytosis, and lactic acidosis were seen in both cohorts, but patients with COVID-19 FM were more tachycardic and hypotensive. Histologically, lymphocytic myocarditis dominated both subsets, with some cases of eosinophilic myocarditis in both cohorts. Cellular necrosis was seen in 44.0% and 47.8% of COVID-19 FM and COVID-19 vaccine FM, respectively. Vasopressors and inotropes were used in 69.9% of COVID-19 FM and in 63.0% of the COVID-19 vaccine FM. Cardiac arrest was observed more in COVID-19 FM (p = 0.008). Venoarterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiogenic shock was also used more commonly in the COVID-19 fulminant myocarditis group (p = 0.0293). Reported mortality was similar (27.7%) and 27.8%, respectively) but was likely worse for COVID-19 FM as the outcome was still unknown in 11% of cases. CONCLUSIONS: In the first series to retrospectively assess fulminant myocarditis associated with COVID-19 infection versus COVID-19 vaccination, we found that both conditions had a similarly high mortality rate, while COVID-19 FM had a more malignant course with more symptoms on presentation, more profound hemodynamic decompensation (higher heart rate, lower blood pressure), more cardiac arrests, and higher temporary MCS requirements including VA-ECMO. In terms of pathology, there was no difference in most biopsies/autopsies that demonstrated lymphocytic infiltrates and some eosinophilic or mixed infiltrates. There was no predominance of young males in COVID-19 vaccine FM cases, with male patients representing only 40.9% of the cohort.

Impact of exercise on pulmonary artery pressure in patients with heart failure using an ambulatory pulmonary artery pressure monitor.

Background: In this multicenter prospective study, we explored the relationship between pulmonary artery pressure (PAP) at rest and in response to a 6-min walk test (6MWT) in ambulatory patients with heart failure (HF) with an implantable PAP sensor (CardioMEMS, Abbott). Methods: Between 5/2019 and 2/2021, HF patients with a CardioMEMS sensor were recruited from seven sites. PAP was recorded in the supine and seated position at rest and in the seated position immediately post-exercise. Results: In our cohort of 66 patients, mean age was 70 ± 12 years, 67% male, left ventricular ejection fraction (LVEF) < 50% in 53%, mean 6MWT distance was 277 ± 95 meters. Resting seated PAPs were 31 ± 15 mmHg (systolic), 13 ± 8 mmHg (diastolic), and 20 ± 11 mmHg (mean). The pressures were lower in the seated rather than the supine position. After 6MWT, the pressures increased to PAP systolic 37 ± 19 mmHg (p < 0.0001), diastolic 15 ± 10 mmHg (p = 0.006), and mean 24 ± 13 mmHg (p < 0.0001). Patients with elevated PAP diastolic at rest (>15 mmHg) demonstrated a greater increase in post-exercise PAP. Conclusion: The measurement of PAP with CardioMEMS is feasible immediately post-exercise. Despite being well-managed, patients had severely limited functional capacity. We observed a significant increase in PAP with ambulation which was greater in patients with higher baseline pressures.

Myocarditis following COVID-19 vaccination in adolescents and adults: a cumulative experience of 2021.

Clinical course and outcomes of myocarditis after COVID-19 vaccination remain variable. We retrospectively collected data on patients > 12 years old from 01/01/2021 to 12/30/2021 who received COVID-19 messenger RNA (mRNA) vaccination and were diagnosed with myocarditis within 60 days of vaccination. Myocarditis cases were based on case definitions by authors. We report on 238 patients of whom most were male (n = 208; 87.1%). The mean age was 27.4 ± 16 (range 12-80) years. Females presented at older ages (41.3 ± 21.5 years) than men 25.7 ± 14 years (p = 0.001). In patients > 20 years of age, the mean duration from vaccination to symptoms was 4.8 days ± 5.5 days, but in < 20, it was 3.0 ± 3.3 days (p = 0.04). Myocarditis occurred most commonly after the Pfizer-BioNTech mRNA vaccine (n = 183; 76.45) and after the second dose (n = 182; 80%). Symptoms started 3.95 ± 4.5 days after vaccination. The commonest symptom was chest pain (n = 221; 93%). Patients were treated with non-steroidal anti-inflammatory drugs (n = 105; 58.3%), colchicine (n = 38; 21.1%), or glucocorticoids (n = 23; 12.7%). About 30% of the patients had left ventricular ejection fraction but more than half recovered the on repeat imaging. Abnormal cardiac MRIs were common; 168 patients (96% of 175 patients that had MRI) had late gadolinium enhancement, while 120 patients (68.5%) had myocardial edema. Heart failure guideline-directed medical therapy use was common (n = 27; 15%). Eleven patients had cardiogenic shock; and 4 patients required mechanical circulatory support. Five patients (1.7%) died; of these, 3 patients had endomyocardial biopsy/autopsy-confirmed myocarditis. Most cases of COVID-19 vaccine myocarditis are mild. Females presented at older ages than men and duration from vaccination to symptoms was longer in patients > 20 years. Cardiogenic shock requiring mechanical circulatory support was seen and mortality was low. Future studies are needed to better evaluate risk factors, and long-term outcomes of COVID-19 mRNA vaccine myocarditis.

Sacubitril/Valsartan Off-Label Uses for Heart Failure.

Sacubitril/valsartan is an angiotensin receptor/neprilysin inhibitor that the Food and Drug Administration has indicated to reduce the risk of cardiovascular hospitalization and death in patients with left ventricular ejection fraction below normal and with no specified ejection-fraction cut-off. However, clinically significant patient groups were excluded or minimally represented in sacubitril/valsartan's pivotal clinical trials. Clinicians often encounter scenarios in which a sacubitril/valsartan off-label use may be beneficial, but limited resources are available to evaluate the efficacy and safety in these patients. This state-of-the-art review describes contemporary literature for sacubitril/valsartan Food and Drug Administration off-label indications to help clinicians assess its appropriateness in these selected, clinically important groups of patients: those with acute decompensated heart failure, acute coronary syndrome, peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, adult congenital heart disease, cardiomyopathy in dialysis patients, right ventricular failure, or durable left ventricular assist device.

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.

New onset nonischemic cardiomyopathy post liver transplantation.

A new onset acute heart failure (HF) with a sudden drop in the left ventricular ejection fraction (LVEF) post orthotopic liver transplant (LT) is a rare but a potentially fatal complication. Because in most of the cases there is no evidence of coronary thrombosis, it can be classified as nonischemic cardiomyopathy. More specifically, clinical presentation of this syndrome shares many features with stress-induced or takotsubo cardiomyopathy. The known factors that predispose these patients to acute HF during or shortly after LT include cirrhotic cardiomyopathy, rapid hemodynamic changes during LT surgery, and the large concentrations of catecholamines, either administered or released endogenously during surgery. The hemodynamic changes during surgery, such as the drop in preload during the anhepatic phase (occasionally requiring massive transfusions and vasopressors) and subsequent increase in preload with acidic and hyperkalemic plasma in the reperfusion phase, lead to rapid electrolyte and hemodynamic shifts. In several cases, intraoperative onset of HF, with or without ventricular arrythmia, could be timed to the reperfusion phase (and occasionally in the anhepatic and pre-anhepatic phases). In other cases, the HF syndrome started hours to days post-surgery. Recovery of cardiac function occurred in the majority of patients during the same admission; however, these patients generally need significantly longer hospitalizations and aggressive supportive care (occasionally requiring mechanical ionotropic and ventilatory support). If recover, the patients have a similar 1-year mortality as those LT patients that did not have this complication. Because no reliable risk stratification currently exists, intraoperative transesophageal echocardiography might be the most dependable way of detecting and addressing this syndrome promptly. Given the mechanism of takotsubo cardiomyopathy, beta-blockade and a preferential use of non-catecholaminergic vasopressors may be a reasonable way to manage this syndrome.

Titin-truncating mutations associated with dilated cardiomyopathy alter length-dependent activation and its modulation via phosphorylation.

AIMS: Dilated cardiomyopathy (DCM) is associated with mutations in many genes encoding sarcomere proteins. Truncating mutations in the titin gene TTN are the most frequent. Proteomic and functional characterizations are required to elucidate the origin of the disease and the pathogenic mechanisms of TTN-truncating variants. METHODS AND RESULTS: We isolated myofibrils from DCM hearts carrying truncating TTN mutations and measured the Ca2+ sensitivity of force and its length dependence. Simultaneous measurement of force and adenosine triphosphate (ATP) consumption in skinned cardiomyocytes was also performed. Phosphorylation levels of troponin I (TnI) and myosin binding protein-C (MyBP-C) were manipulated using protein kinase A and λ phosphatase. mRNA sequencing was employed to overview gene expression profiles. We found that Ca2+ sensitivity of myofibrils carrying TTN mutations was significantly higher than in myofibrils from donor hearts. The length dependence of the Ca2+ sensitivity was absent in DCM myofibrils with TTN-truncating variants. No significant difference was found in the expression level of TTN mRNA between the DCM and donor groups. TTN exon usage and splicing were also similar. However, we identified down-regulation of genes encoding Z-disk proteins, while the atrial-specific regulatory myosin light chain gene, MYL7, was up-regulated in DCM patients with TTN-truncating variants. CONCLUSION: Titin-truncating mutations lead to decreased length-dependent activation and increased elasticity of myofibrils. Phosphorylation levels of TnI and MyBP-C seen in the left ventricles are essential for the length-dependent changes in Ca2+ sensitivity in healthy donors, but they are reduced in DCM patients with TTN-truncating variants. A decrease in expression of Z-disk proteins may explain the observed decrease in myofibril passive stiffness and length-dependent activation.

Lymphocytic myocarditis with suspected granulomatosis with polyangiitis presenting as cardiogenic shock, restrictive cardiomyopathy and complete heart block.

We report a case of restrictive cardiomyopathy from lymphocytic myocarditis in a patient with suspected granulomatosis with polyangiitis (GPA). The case was complicated by complete heart block and renal failure. The diagnosis was supported by upper airway involvement, elevated serum serine proteinase 3 antibodies, and endomyocardial biopsy with lymphocytic infiltration. The patient responded appropriately to aggressive immunosuppressive therapy. .

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.

Randomized Trial of Lisinopril Versus Carvedilol to Prevent Trastuzumab Cardiotoxicity in Patients With Breast Cancer.

BACKGROUND: Trastuzumab is highly effective for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer but is associated with a decline in left ventricular ejection fraction. OBJECTIVES: The purpose of this study was to determine whether angiotensin-converting enzyme inhibitors or beta-blockers reduce the rate of trastuzumab-induced cardiotoxicity (left ventricular ejection fraction decrease >10%, or >5% if below 50%) and limit treatment interruptions. METHODS: In this double-blind, multicenter, placebo-controlled trial, cardiotoxicity and treatment interruptions in patients with HER2-positive breast cancer treated with trastuzumab for 12 months were evaluated over a 2-year period. Patients were stratified by anthracycline use and then randomized to receive lisinopril, carvedilol, or placebo. RESULTS: The study included 468 women, age 51 ± 10.7 years. For the entire cohort, cardiotoxicity was comparable in the 3 arms and occurred in 32% of patients on placebo, 29% on carvedilol, and 30% on lisinopril. For patients receiving anthracyclines, the event rates were higher in the placebo group (47%) than in the lisinopril (37%) and the carvedilol (31%) groups. Cardiotoxicity-free survival was longer on both carvedilol (hazard ratio: 0.49; 95% confidence interval: 0.27 to 0.89; p = 0.009) and lisinopril (hazard ratio: 0.53; 95% confidence interval: 0.30 to 0.94; p = 0.015) than on placebo. In the whole cohort, as well as in the anthracycline arm, patients on active therapy with either angiotensin-converting enzyme inhibitor or beta-blockers experienced fewer interruptions in trastuzumab than those on placebo. CONCLUSIONS: In patients with HER2-positive breast cancer treated with trastuzumab, both lisinopril and carvedilol prevented cardiotoxicity in patients receiving anthracyclines. For such patients, lisinopril or carvedilol should be considered to minimize interruptions of trastuzumab. (Lisinopril or Coreg CR in Reducing Side Effects in Women With Breast Cancer Receiving Trastuzumab; NCT01009918).

Left ventricular assist device-related infections: does the time of onset matter?

A frequent complication of left ventricular assist devices (LVAD) is the LVAD-associated infections (LVADIs). Contamination may occur during initial surgery/admission or at a later time. We studied the clinical manifestations and outcomes of LVADIs depending on the time of the onset. Patients implanted with LVADs at our institution between August 2009 and December 2014 were included. Patients were stratified into 2 groups based on whether the infection occurred early (< 180 days) or late (≥ 180 days) after LVAD implantation. Out of 37 overall LVADI episodes, 16 (43%) and 21 (57%) occurred early or late after device implantation, respectively. Median time to first LVADI was 88 ± 35 vs. 456 ± 187 days between groups. While superficial driveline-related infection was the most common LVADI type for both groups (56 vs. 71%, p = 0.489), driveline drainage was more prevalent in the late group (24 vs. 69%; p = 0.009). Early LVADIs involved more gram-positive flora, mostly Staphylococcus aureus (69 vs. 33%, p = 0.049), whereas late LVADIs involved more gram-negative pathogens, mostly Pseudomonas aueroginosa (25 vs. 57%; p = 0.045). High rates of treatment failure were consistent between groups (88 vs. 71%, p = 0.384). Compared with superficial LVADI, deeper infections were associated with an increase in mortality (13 vs 46%, p = 0.046). We concluded that early onset with likely in-hospital contamination involved more gram-positive flora, whereas late infection involved more gram-negative flora. Regardless of timing, success of antibacterial treatment was dismal, and infection depth correlated with poorer outcomes.

Trends in the Incidence and In-Hospital Outcomes of Patients With Atrial Fibrillation Complicated by Non-ST-Segment Elevation Myocardial Infarction.

Atrial fibrillation (AF) can present with non-ST-segment elevation myocardial infarction (NSTEMI). The incidence, characteristics, outcomes, and treatment of this subgroup of patients with AF remains poorly studied. Using data from the National Inpatient Sample database, we (1) compared baseline characteristics of patients with AF with/without NSTEMI, (2) evaluated their outcomes and associated trends over the study period (2004-2013), and (3) evaluated revascularization (by percutaneous coronary intervention or coronary artery bypass graft [CABG]) and the impact on patient outcomes. Of the 3 923 436 patients admitted with a primary diagnosis of AF, 47 785 (1.2%) had a secondary diagnosis of NSTEMI. In this subgroup with AF and NSTEMI, there was a significant trend toward a decrease in mortality ( P = .002), stroke ( P < .001), and gastrointestinal bleeding ( P < .001) during the study period. Compared to unrevascularized patients, revascularized patients were more likely to be younger (72.2 ± 10.2 vs 77.0 ± 11.8 years old, P < .001), male (57.8 vs 42.7%, P < .001), and had a much higher incidence of coronary risk factors. Revascularization was associated with increased survival in multivariable analysis (odds ratio: 0.562, 95% confidence interval: 0.334-0.946, P = .03). In conclusion, among patients admitted with AF, 1.2% were diagnosed with NSTEMI. A minority of patients with AF and NSTEMI underwent revascularization and had better in-hospital outcomes.

Impact of Aortic Valve Replacement on Glycemic Control in Diabetes Mellitus.

Introduction: The Framingham Studies revealed that diabetes mellitus (DM) predisposed subjects to a two- to eight-fold increase in the risk of developing heart failure (HF). However, there is much less information available about the reverse issue; namely, whether there is an increased risk of developing DM in patients with HF. We sought to determine if reversal or partial reversal of HF through aortic valve replacement (AVR) would improve glycemic control in patients with DM at our institution. Methods: The electronic medical records of 57 consecutive diabetic patients were retrospectively analyzed. These patients had undergone AVR at a medium-sized academic medical center from May 2005 through May 2015, and had glycated hemoglobin (HbA1C) measured before and after the procedure. The variables of interest included HbA1C, and echocardiographic parameters such as left ventricular ejection fraction (LVEF), tricuspid regurgitation velocity (TRV), and right ventricular systolic pressure (RVSP) before and after valve replacement. Results: HbA1C decreased significantly during the first year after replacement, from 7.1% (range 4.4 - 13.0%) before surgery to 6.5% in the first year (P < .05). In addition, the calculated RVSP decreased from 44 mmHg (20 - 79 mmHg) to 37 mmHg (P < .05 from the preoperative value). LVEF and TRV did not change significantly. Reductions in HbA1C and RVSP during the first year were greater in patients who experienced an increase of 5% or more in EF at their first postoperative measurement. Patients with higher baseline HbA1C values had a greater decline in glycated Hb during the first year (P < .01). Conclusion: AVR was associated with a reduction of HbA1C and a decrease in pulmonary artery systolic pressure within one year of the procedure.