Search

Background: The long-term contemporary outcomes of patients with immune checkpoint inhibitor (ICI) myocarditis, spanning the spectrum of clinical severity, are undetermined., Objectives: We sought to investigate the characteristics and cardiovascular outcomes of patients with severe and nonsevere ICI myocarditis., Methods: This was a retrospective cohort study of patients with suspected ICI myocarditis at Massachusetts General Brigham Health System conducted between 2015 and 2022. Cases were classified as severe, nonsevere, and negative based on the International Cardio-Oncology Society criteria. One-year cardiovascular mortality, all-cause mortality, and cardiovascular readmissions were evaluated. We also evaluated 1-year ICI resumption and left ventricular ejection fraction over a median follow-up of 18 (Q1-Q3: 8-67) weeks., Results: The study included 160 patients: 28 severe, 96 nonsevere, and 36 negative cases. Patients with severe myocarditis had an increased risk of 1-year cardiovascular mortality, particularly in the early post-myocarditis period (29% vs 5%; HR: 6.52; 95% CI: 2.2-19.6; P  < 0.001). Patients with nonsevere myocarditis had a cardiovascular mortality rate similar to negative cases (HR: 0.61; 95% CI: 0.14-2.54). One-year all-cause mortality did not differ between severe, nonsevere, and negative cases ( P  = 0.74). Rates of 1-year cardiovascular readmissions and long-term left ventricular ejection fraction were also similar among the 3 groups. ICI resumption was low, even in negative cases., Conclusions: In a contemporary analysis of patients with suspected ICI myocarditis, severe ICI myocarditis was associated with increased 1-year cardiovascular mortality, which was lower than previously reported. Patients with nonsevere ICI myocarditis had outcomes similar to negative cases. The optimal management strategies for nonsevere ICI myocarditis need to be re-evaluated., Competing Interests: Dr Nohria is supported by the Catherine Goff Fitch fund and the Gelb Master Clinician fund at Brigham and Women’s Hospital. Dr Nohria receives research support from Bristol Myers Squibb; and consulting fees from Altathera Pharmaceuticals, AstraZeneca, Bantam Pharmaceuticals, Regeneron Pharmaceuticals, and Takeda Oncology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Aims: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are used increasingly for patients with heart failure or chronic kidney disease to improve cardiac and renal outcomes. The use of these medications in patients with left ventricular assist devices (LVAD) is still limited and lacks evidence regarding the safety profile. In this study, we aimed to report our experience in treating 20 patients, supported by LVAD, with SGLT2 inhibitors., Methods: We studied the safety profile of SGLT2 inhibitors (dapagliflozin and empagliflozin) in 20 patients (mean age 64.7 ± 12.2 years, 75% male) supported by LVAD as destination therapy. All patients have diabetes mellitus and were prescribed SGLT2 inhibitors for glycemic control., Results: SGLT2 inhibitors were well tolerated with no major adverse events. Few suction events were reported in three patients without the need for pump speed adjustment. There was no change in mean arterial pressure (71.1 ± 5.6 vs. 70.1 ± 4.8 mmHg, P  = 0.063). Modest decline in renal function was observed in six patients within the first weeks after drug initiation. There were no events of diabetic ketoacidosis or limb amputation., Conclusion: SGLT2 inhibitors are safe in patients with LVAD and may potentially improve cardiovascular and renal outcomes in this special population., (Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.)

To examine the role of acute coronary syndrome (ACS) in subsequent cancer incidence and survival, 2 cohorts of patients hospitalized with ACS were matched 1:1 by gender and age (±3 years) to cardiovascular disease (CVD)-free patients from 2 cycles of the Israeli National Health and Nutrition Surveys. Data on all-cause mortality were retrieved from national registries. Cancer incidence with death treated as a competing event, overall survival, and mortality risk associated with incident cancer as a time-dependent variable were compared between the groups. Our cohort included 2,040 cancer-free matched pairs (mean age of 60±14 years, 42.5% women). Despite higher rates of smokers and patients with hypertension and diabetes mellitus, 10-year cumulative cancer incidence was significantly lower in the ACS group compared with CVD-free group (8.0% vs 11.4%, p = 0.02). This decreased risk was more pronounced in women than men (p interaction  = 0.05). Although being free of CVD meant a significant (p <0.001) survival advantage in the general cohort, this advantage faded once a cancer diagnosis was made (p = 0.80). After adjustment for sociodemographic and clinical covariates, the hazard ratios for mortality associated with a cancer diagnosis were 2.96 (95% confidence interval: 2.36 to 3.71) in the ACS group versus 6.41 (95% confidence interval: 4.96 to 8.28) in the CVD-free group (P interaction <0.001). In conclusion, in this matched cohort, ACS was associated with a lower risk of cancer and mitigated the excess risk of mortality associated with cancer incidence., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Left ventricular assist devices (LVADs) support the hearts of patients with advanced heart failure. Following LVAD implantation, patients face a complex regimen of self-care behaviours including self-care maintenance, self-care monitoring and self-care management. However, during the COVID-19 pandemic, symptoms of anxiety and depression may have interfered with their self-care. Currently, little is known on how specific self-care behaviours of LVAD-implanted patients changed during the COVID-19 pandemic. We aim to describe the changes in self-care behaviours among patients with an implanted LVAD in Israel during the COVID-19 pandemic and explore the factors related to self-care behaviour change., Methods: A prospective observational cross-sectional study design. A convenience sample of 27 Israeli LVAD-implanted patients (mean age 62.4 ± 9, 86% male, 78.6% living with a partner) completed the LVAD Self-Care Behaviour Scale (1 = never to 5 = always) and Hospital Anxiety and Depression Scale (0 = not at all to 3 = most of the time). Data were collected before and after the onset of the COVID-19 pandemic in Israel. Statistical analyses included paired t-tests, Pearson's correlations, and one-way repeated measures ANOVAs., Results: During the COVID-19 pandemic, a significant decrease was found in patients' adherence to checking and recording their LVAD speed, flow, power and PI (Pulsatility Index) (P = 0.05), checking their INR (P = 0.01), and daily weighing (P < 0.01). The prevalence of some behaviours (e.g. regularly exercising) increased in some patients and decreased in others. Patients living without a partner worsened their adherence to some of the self-care behaviours (e.g. taking medicines as prescribed), compared with those living with a partner (M b  = 5.0 ± 0 and M d  = 5.0 ± 0, delta = 0 vs. M b  = 5.0 ± 0 and M d  = 4.6 ± 0.9, delta = -0.4, respectively; F = 4.9, P = 0.04). Women, and not men, tended to improve their adherence to the self-care behaviour such as avoiding kinking, pulling, or moving the LVAD driveline at the exit site (M b  = 4.0 ± 1.0 and M d  = 5.0 ± 0, delta = 1.0 vs. M b  = 4.5 ± 0.9 and M d  = 4.4 ± 1.2, delta = -0.1, F = 4.7, P = 0.04, respectively). In total, 41% (11) patients reported neither anxiety nor depression, 11% (3) reported anxiety, 15% (4) reported depression, and 44% (12) reported both anxiety and depression. No associations between anxiety and/or depression and self-care behaviours were found., Conclusions: Priorities in self-care behaviours among patients with implanted LVAD changed after the onset of the COVID-19 pandemic. Factors that assisted with adherence to self-care behaviours included living with a partner and being female. The current results may guide further research on identifying behaviours that are at risk of not being maintained during a time of emergency., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: A recently published expert consensus document recommended a multiparametric tool to monitor cardiac disease progression in patients with transthyretin cardiac amyloidosis (ATTR-CA). We aimed to evaluate the effect of the transthyretin stabiliser drug, tafamidis, by applying this integrative tool., Methods: We retrospectively applied a multiparametric tool in a group of ATTR-CA patients who were given tafamidis between the years 2019-2021 and were followed in a dedicated clinic. We used three pre-specified follow-up timepoints: at 6, 12 and 18 months., Results: We included 16 ATTR-CA patients (wild-type ( n  = 14) and mutant ( n  = 2)). The median age at the initiation of tafamidis was 76 (IQR 70, 84) years and 75% of study patients were classified as NYHA functional class 2 or 3. All patients had elevated levels of high-sensitive troponin T (median 92 (IQR 63, 115) ng/L) and NT-proBNP (median 3784 (2290, 8773) pg/mL). At the end of 18-month follow-up, two patients have suffered from high-grade atrioventricular block and required permanent pacing, and one patient had heart-failure-related admission. Twenty-five percent and 50% of patients were classified as NYHA Class 1 at the initiation of tafamidis and at 18-months treatment, respectively. No patient was defined with disease progression at 6- or 12-month follow up; however, one patient (14%) was defined with a deteriorated disease status at 18-month follow-up., Conclusions: Based on a multiparametric tool, the use of tafamidis promoted disease stabilisation in the majority of patients at 18-month follow-up. Further study should focus on monitoring disease improvement in patients with ATTR-CA.

Aims: This study aimed to characterize the final diagnosis and prognosis of patients with grade 1 myocardial scintigraphy uptake, which is an unequivocal result for the diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) requiring further invasive investigation with tissue biopsy., Methods and Results: We retrospectively compared the clinical and imaging parameters of patients suspected for ATTR-CA (based on clinical and echocardiographic parameters) with grade 1 vs. grades 2/3 technetium pyrophosphate uptake on cardiac scintigraphy. Prospectively, grade 1 patients underwent re-evaluation for ATTR-CA at long term. Of the 132 ATTR-CA suspected patients, 89 (67%) were diagnosed as grade 1 and 43 (33%) as grades 2/3 uptake. Grade 1 vs. grades 2/3 patients were younger and female predominant with lower biomarker levels and left ventricular mass. Based on available imaging and pathology findings, only 6 out of the 89 patients with grade 1 uptake (7%) were finally diagnosed with light-chain cardiac amyloidosis, whereas no patient was diagnosed with ATTR-CA. At 2 [interquartile range (IQR) 0.75, 3.25] years of follow-up, the survival of patients with grade 1 vs. grades 2/3 uptake was significantly better [hazard ratio 0.271 (95% confidence interval 0.130 to 0.563, P = 0.0005)]. Prospectively, 30 patients with grade 1 uptake were re-evaluated at a median follow-up of 3.2 (IQR 2.2, 3.9) years. Their New York Heart Association class, biomarker levels, and echocardiography findings remained stable. No patient (0/25) demonstrated grades 2/3 uptake at repeated long-term scintigraphy., Conclusions: Patients with suspected ATTR-CA and a grade 1 scintigraphy uptake demonstrate a stable clinical, laboratory, imaging, and scintigraphy phenotype along with a benign survival profile at long-term follow-up. Larger studies should define the optimal evaluation strategy in this population., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Data are limited regarding the characteristics and outcomes of patients with cancer who are found eligible for primary defibrillator therapy. We performed a single-center retrospective analysis of patients with preexisting cancer diagnoses who become eligible for a primary prevention implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) defibrillator. Multicenter Automatic Defibrillator Implantation Trial-ICD (MADIT-ICD) benefit scores were calculated. The study included 75 cancer patients at a median age of 73 (interquartile range 64, 81) years at heart failure diagnosis. Active cancer was present in 51%. Overall, 55% of the cohort had coronary artery disease and 37% were CRT eligible. We found that 48%, 49%, and 3% of cohorts had low, intermediate, and high MADIT-ICD Benefit scores, respectively. Only 27% of patients underwent primary defibrillator implantation. Using multivariate analysis, indication for CRT and intermediate/high MADIT-ICD Benefit categories were found as independent predictors for implantation (odds ratio 8.42 p <0.001 and odds ratio 3.74 p = 0.040, respectively). During a median follow-up of 5.3 (interquartile range 4.5, 7.2) years, one patient (5%) with a defibrillator had appropriate shock therapy and 2 patients (10%) had bacteremia. Of 13 patients with CRT defibrillator-implants, one patient was admitted for heart failure exacerbation (8%). Using a time-varying covariate model, we did not observe statistically significant differences in the survival of patients with cancer implanted versus those not implanted with primary defibrillators (hazard ratio 0.521, p = 0.127). In conclusion, although primary defibrillator therapy is underutilized in patients with cancer, its relative benefit is limited because of competing risk of nonarrhythmic mortality. These findings highlight the need for personalized cardiologic and oncologic coevaluation., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Dr Nohria has received research support from Bristol Myers Squibb; and is a consultant for AstraZeneca, Bantam Pharmaceuticals, and Takeda Oncology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: It is unclear whether newly diagnosed cancer adds to the risk of arterial thromboembolism (ATE) in patients with atrial fibrillation/flutter (AF). This is especially relevant for AF patients with low to intermediate CHA 2 DS 2 -VASc scores in whom the risk-benefit ratios between ATE and bleeding are delicately balanced., Objectives: The objectives were to evaluate the ATE risk in AF patients with a CHA 2 DS 2 -VASc score of 0 to 2 with and without cancer., Methods: A population-based retrospective cohort study was performed. Patients with a CHA 2 DS 2 -VASc score of 0 to 2 not receiving anticoagulation at cancer diagnosis (or the matched index date) were included. Patients with embolic ATE or cancer before study index were excluded. AF patients were categorized into AF and cancer and AF and no cancer cohorts. Cohorts were matched for multinomial distribution of age, sex, index year, AF duration, CHA 2 DS 2 -VASc score, and low/high/undefined ATE risk cancer. Patients were followed from study index until the primary outcome or death. The primary outcome was acute ATE (ischemic stroke, transient ischemic attack, or systemic ATE) at 12 months using International Classification of Diseases-Ninth Revision codes from hospitalization. The Fine-Gray competing risk model was used to estimate the HR for ATE with death as a competing risk., Results: The 12-month cumulative incidence of ATE was 2.13% (95% CI: 1.47-2.99) in 1,411 AF patients with cancer and 0.8% (95% CI: 0.56-1.10) in 4,233 AF patients without cancer (HR: 2.70; 95% CI: 1.65-4.41). The risk was highest in men with CHA 2 DS 2 -VASc = 1 and women with CHA 2 DS 2 -VASc = 2 (HR: 6.07; 95% CI: 2.45-15.01)., Conclusions: In AF patients with CHA 2 DS 2 -VASc scores of 0 to 2, newly diagnosed cancer is associated with an increased incidence of stroke, transient ischemic attack, or systemic ATE compared with matched controls without cancer., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Purpose: Immune checkpoint blocker (ICB) associated myocarditis (ICB-myocarditis) may present similarly and/or overlap with other cardiac pathology including acute coronary syndrome presenting a challenge for prompt clinical diagnosis., Methods: An international registry was used to retrospectively identify cases of ICB-myocarditis. Presence of coronary artery disease (CAD) was defined as coronary artery stenosis >70% in patients undergoing coronary angiogram., Results: Among 261 patients with clinically suspected ICB-myocarditis who underwent a coronary angiography, CAD was present in 59/261 patients (22.6%). Coronary revascularization was performed during the index hospitalisation in 19/59 (32.2%) patients. Patients undergoing coronary revascularization less frequently received steroids administration within 24 h of admission compared to the other groups (p = 0.029). Myocarditis-related 90-day mortality was 9/17 (52.7%) in the revascularised cohort, compared to 5/31 (16.1%) in those not revascularized and 25/156 (16.0%) in those without CAD (p = 0.001). Immune-related adverse event-related 90-day mortality was 9/17 (52.7%) in the revascularized cohort, compared to 6/31 (19.4%) in those not revascularized and 31/156 (19.9%) in no CAD groups (p = 0.007). All-cause 90-day mortality was 11/17 (64.7%) in the revascularized cohort, compared to 13/31 (41.9%) in no revascularization and 60/158 (38.0%) in no CAD groups (p = 0.10). After adjustment of age and sex, coronary revascularization remained associated with ICB-myocarditis-related death at 90 days (hazard ratio [HR] = 4.03, 95% confidence interval [CI] 1.84-8.84, p < 0.001) and was marginally associated with all-cause death (HR = 1.88, 95% CI, 0.98-3.61, p = 0.057)., Conclusion: CAD may exist concomitantly with ICB-myocarditis and may portend a poorer outcome when revascularization is performed. This is potentially mediated through delayed diagnosis and treatment or more severe presentation of ICB-myocarditis., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LL has served on the advisory board for Daiichi Sankyio, Senaca, Astra Zeneca and Servier, as an external expert for Astra Zeneca and received speakers' honoraria from Novartis and MSD. LL is receiving grants from the German Center for Cardiovascular Research (DZHK), German Reuter Foundation (DFG) LE3570/2-1; 3570/3-1 and grant 01KC2006B from the Federal Ministry for Education and Research (BMBF). DA received speakers’ honoraria from BMS, Ipsen and participated to ad-boards from Sanofi and AstraZeneca. KT has received honoraria from Bristol Myers Squibb, Pfizer, Ono Pharmaceutical, Merck BioPharma, Bayer, and grants from Otsuka, Daiichi, Sankyo and Takeda. JM has served on advisory boards for Bristol Myers Squibb, Takeda, Regeneron, Audentes, Deciphera, Ipsen, Janssen, ImmunoCore, Boston Biomedical, Amgen, Myovant, Triple Gene/Precigen, Cytokinetics and AstraZeneca and supported by NIH grants (R01HL141466, R01HL155990, R01HL156021). JES have received consultancy fees from BMS, BeiGene, AstraZeneca, Novartis, and grants from BMS, Novartis, French Agence Nationale de la Recherche, Fondation Coeur et Recherche, Fédération Française de Cardiologie. All other authors have nothing to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The immunogenicity of two-dose severe acute respiratory syndrome coronavirus 2 vaccine is lower among heart transplant (HTx) recipients, compared with the general population. Our aim was to assess the immunogenicity of a third-dose vaccine in HTx recipients., Methods: This is a prospective cohort study of HTx recipients who received a third dose of the BNT162b2 vaccine. Immunogenicity was assessed by serum levels of anti-spike immunoglobulin G (S-IgG), taken at baseline and 14-28 days after the third dose. Titres above 50 U/ml were interpreted positive., Results: We Included 42 HTx recipients at a median age of 65 years [interquartile range (IQR) 58-70]. At baseline, the median of 27 days (IQR 13-42) before the third dose and the median titre of the whole group was 18 U/ml (IQR 4-130). Only 14 patients (33%) were S-IgG seropositive. After the third dose, the proportion of seropositive patients increased significantly to 57% (P = 0.05) and the median titre increased significantly to 633 U/ml (IQR 7-6104, P < 0.0001). Younger age at HTx (OR per 1-year decrease 1.07, P = 0.05), low tacrolimus serum level (OR per 1-unit decrease 2.28, P = 0.02), mammalian target of rapamycin use (OR 13.3, P = 0.003), lack of oral steroids use (OR 4.17, P = 0.04) and lack of calcineurin inhibitor use (71% of responders vs 100% non-responders received calcineurin inhibitors, P = 0.01) were predictors of seropositive result after the third dose. However, no significant association was detected following adjustment for baseline S-IgG titre., Conclusions: Third-dose booster of BNT162b2 vaccine significantly increased immunogenicity among HTx recipients who previously received a two-dose vaccine., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Endothelial microvascular dysfunction is a known mechanism of vascular pathology in cardiac amyloidosis (CA). Scientific evidence regarding the possible protective role of the amyloid transthyretin (ATTR) stabilizer, tafamidis, is lacking. Circulating endothelial progenitor cells (cEPCs) have an important role in the process of vascular repair. We aimed to examine the effect of tafamidis on cEPCs., Methods and Results: Study population included patients with ATTR-CA. cEPCs were assessed using flow cytometry by the expression of CD34 (+) /CD133 (+) and vascular endothelial growth factor receptor (VEGFR)-2 (+) and by the formation of colony-forming units (CFUs) and production of VEGF. Tests were repeated at pre-specified time-points up to 12 months following the initiation of tafamidis. Included were 18 ATTR-CA patients at a median age of 77 (IQR 71, 85) years and male predominance (n = 15, 83%). Following the initiation of tafamidis and during 12 months of drug treatment, there was a gradual increase in the levels of CD34 (+) /VEGFR-2 (+) (0.43 to 2.42% (IQR 1.53, 2.91)%, p = 0.002) and CD133 (+) /VEGFR-2 (+) (0.49 to 1.64% (IQR 0.97, 2.90)%, p = 0.004). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with tafamidis (from 0.5 CFUs (IQR 0.0, 1.0) to 3.0 (IQR 1.3, 3.8) p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (from 0.12 (IQR 0.03, 0.16) to 0.30 (IQR 0.18, 0.33), p < 0.001). VEGF levels increased following treatment (from 54 (IQR 52, 72) to 107 (IQR 62, 129) pg/ml, p = 0.039)., Conclusions: Tafamidis induced the activation of the cEPCs pathway, possibly promoting endothelial repair in ATTR-CA., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

This paper reviews the current evidence on the pathogenesis, clinical manifestations, diagnosis and management of cancer-associated non-bacterial thrombotic endocarditis (NBTE). NBTE is an underdiagnosed condition characterized by sterile valvular vegetations composed of platelets and fibrin which are susceptible to systemic embolization. Cancer is a leading cause of NBTE and should be excluded in NBTE cases without a clear etiology. Malignancies most frequently associated with NBTE are mucin-releasing adenocarcinomas of the lung, ovary, biliary system, pancreas, breast and stomach. NBTE carries a high risk of arterial thromboembolism, while cardiac valvular dysfunction is much less frequent. NBTE appears to be an important underdiagnosed cause of cancer-associated embolic stroke of undetermined source. Characteristics associated with cancer-associated NBTE include elevated D-dimer, visceral infarcts, cerebral infarcts in multiple vascular territories, transcranial doppler microembolic signals, disseminated cancer and adenocarcinoma histology. Transesophageal echocardiography is the diagnostic test of choice, and all suspected cases should be evaluated for the presence of elevated D-dimers and disseminated intravascular coagulation. Long-term anticoagulation with low molecular weight heparin should be strongly considered, and surgical intervention is usually not needed. Underlying cancer must be diagnosed swiftly (if previously undiagnosed) and anti-cancer treatment should be initiated as soon as possible. The paucity of data regarding all aspects of NBTE, and the severe clinical consequences of untreated NBTE, are an urgent call for future research., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We aimed to describe the natural history of left ventricular assist device (LVAD)-supported patients with preimplantation significant tricuspid regurgitation (TR) in a single-center retrospective analysis of LVAD-implanted patients (2008-2019). TR severity was assessed semiqualitatively using color-Doppler flow: insignificant TR (iTR) was defined as none/mild TR and significant TR (sTR) as ≥moderate TR. Included were 121 LVAD-supported patients of which 53% (n = 64) demonstrated sTR preimplantation. Among patients with pre-LVAD implantation sTR and available echocardiographic data, 55% (n = 26) ameliorated their TR severity grade to iTR during the first-year postsurgery and 55% (n = 17) had iTR at 2-year follow-up. On univariate analysis, predictors for TR severity improvement post-LVAD implantation were preimplant lack of atrial fibrillation, reduced inferior vena cavae diameter, and elevated pulmonary vascular resistance. In patients who failed to improve their TR severity grade, we observed a deterioration in right ventricular (RV) function (pulmonary artery pressure index 2.0 [1.7, 2.9], a decline in RV work index 242 [150, 471] mm Hg·L/m2) and higher loop-diuretics dose requirement. At a median of 21 (IQR 8, 40) months follow-up, clinical LVAD-related complications, heart failure-hospitalizations, and overall survival were similar among patients who improved versus failed to improve their TR severity-grade post-LVAD implantation. In conclusion, LVAD implantation is accompanied by a reduction in TR severity in approximately 50% of patients. In patients who failed to improve their TR severity grade, progressive RV dysfunction was observed. Overall, an isolated LVAD implantation in patients with sTR does not adversely affect survival., Competing Interests: Disclosures: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Aims: To assess the 6 months immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplanted (HTx) recipients and left ventricular assist device (LVAD)-supported patients., Methods and Results: A prospective single-centre cohort study of HTx recipients and LVAD-supported patients who received a two-dose SARSCoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech). Whole blood for anti-spike IgG (S-IgG) antibodies were drawn at 6 months after the first vaccine dose. S-IgG data at 6 weeks were available for a subgroup of HTx recipients. S-IgG ≥ 50 AU/mL were interpreted positive. The cohort included 53 HTx recipients and 18 LVAD-supported patients. The median time from HTx or LVAD implantation to the 1 st vaccine dose was 90 (IQR 30, 172) months and 22 (IQR 6, 78) months, respectively. The seropositivity rates of S-IgG antibodies and their titre levels in HTx recipients and LVAD-supported patients were 45% and 83% respectively, (P = 0.006), and 35 (IQR 7, 306) AU/mL and 311 (IQR 86, 774) AU/mL, respectively, (P = 0.006). Reduced SARSCoV-2 vaccine immunogenicity in HTx recipients was associated with older age [odds ratio (OR) 0.917 confidence interval (CI 0.871, 0.966), P = 0.011] and with the use of anti-metabolites-based immunosuppressive regimens [OR 0.224 (CI 0.065, 0.777), P = 0.018]. mTOR inhibitors were associated with higher immunogenicity [OR 3.1 (CI 1.01, 9.65), P = 0.048]. Out of 13 HTx recipients who were S-IgG seropositive at 6 weeks after the first vaccine dose, 85% remained S-IgG seropositive at 6 month follow-up., Conclusions: At 6 months post-vaccination, S-IgG immunogenicity in HTx recipients is low, particularly in older HTx recipients and in those treated with anti-metabolites drugs., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Large vessel vasculitis (LVV) is composed of conditions in which inflammation of blood vessel walls affects mainly large arteries, such as the aorta and its main branches, and in some cases the coronary arteries. Coronary artery involvement in systemic vasculitis is associated with significant morbidity and mortality. We present a case of a young patient diagnosed with extensive coronary disease diagnosed as Takayasu arteritis, when whom a concomitant diagnosis of Hodgkin's lymphoma was made. The literature review revealed ten cases of malignancies associated with Takayasu arteritis. We discuss the complexity of the management of concurrent hematological malignancy with TAK and extensive coronary arteritis. This complicated and cross-disciplinary case also represents the pivotal importance of multi-disciplinary team decision in order to achieve the best clinical outcome of both disorders., (© 2021. International League of Associations for Rheumatology (ILAR).)

The use of immune checkpoint inhibitors (ICIs) as a mono- or adjuvant oncologic treatment is rapidly expanding to most fields of cancer. Alongside their efficacy, ICIs carry the risk of immune-related adverse events (irAEs) arising from misguided immune-mediated response to normal tissues. In the cardiovascular system, the cardiac toxicity of ICIs has been primarily related to the development of an acute, immune-mediated myocarditis; beyond this potentially fatal complication, evidence of an increased risk of cardiovascular events and accelerated atherosclerosis is emerging, as well as reports of other cardiovascular adverse events such as arrythmias, Takotsubo-like syndrome and vascular events. The absence of identified risk factors for cardiotoxic complications, specific monitoring strategies or diagnostic tests, pose challenges to the timely recognition and optimal management of such events. The rising numbers of patients being treated with ICIs make this potential cardiotoxic effect one of paramount importance for further investigation and understanding. This review will discuss the most recent data on different cardiotoxic effects of ICIs treatment.

Purpose: Circulating endothelial progenitor cells (cEPCs) are vital to vascular repair by re-endothelialization. We aimed to explore the effect of proprotein convertase subtilisin kexin type 9 inhibitors (PCSK9i) on cEPCs hypothesizing a possible pleiotropic effect., Methods: Patients with cardiovascular disease (CVD) were sampled for cEPCs at baseline and following the initiation of PCSK9i. cEPCs were assessed using flow cytometry by the expression of CD34 (+) /CD133 (+) and vascular endothelial growth factor receptor (VEGFR)-2 (+) , and by the formation of colony-forming units (CFUs) and production of VEGF., Results: Our cohort included 26 patients (median age 68 (IQR 63, 73) years; 69% male). Following 3 months of treatment with PCSK9i and a decline in low-density lipoprotein cholesterol levels (153 (IQR 116, 176) to 56 (IQR 28, 72) mg/dl), p < 0.001), there was an increase in CD34 (+) /CD133 (+) and VEGFR-2 (+) cell levels (0.98% (IQR 0.37, 1.55) to 1.43% (IQR 0.90, 4.51), p = 0.002 and 0.66% (IQR 0.22, 0.99) to 1.53% (IQR 0.73, 2.70), p = 0.05, respectively). Functionally, increase in EPCs-CFUs was microscopically evident following treatment with PCSK9i (1 CFUs (IQR 0.0, 1.0) to 2.5 (IQR 1.5, 3), p < 0.001) with a concomitant increase in EPC's viability as demonstrated by an MTT assay (0.15 (IQR 0.11, 0.19) to 0.21 (IQR 0.18, 0.23), p < 0.001). VEGF levels increased following PCSK9i treatment (57 (IQR 18, 24) to 105 (IQR 43, 245), p = 0.006)., Conclusions: Patients with CVD treated with PCSK9i demonstrate higher levels of active cEPCs, reflecting the promotion of endothelial repair. These findings may represent a novel mechanism of action of PCSK9i., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of the LVAD-supported patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD-supported patients. The expected and non-expected device-related and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of the LVAD implanting centres. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to experience comorbidities common in the older population. The probability of an LVAD-supported patient presenting with medical emergency to a local emergency department, internal, or surgical ward of a non-LVAD implanting centre is increasing. The purpose of this trilogy is to supply the immediate tools needed by the non-LVAD specialized physician: ambulance clinicians, emergency ward physicians, general cardiologists, internists, anaesthesiologists, and surgeons, to comply with the medical needs of this fast-growing population of LVAD-supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department and from the emergency department to the internal or surgical wards and eventually to the discharge home from the hospital back to the general practitioner. In this first part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, after the introduction on the assist devices technology in general, definitions and structured approach to the assessment of the LVAD-supported patient in the ambulance and emergency department is presented including cardiopulmonary resuscitation for LVAD-supported patients., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The growing population of left ventricular assist device (LVAD)-supported patients increases the probability of an LVAD- supported patient hospitalized in the internal or surgical wards with certain expected device related, and patient-device interaction complication as well as with any other comorbidities requiring hospitalization. In this third part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the hospitalized LVAD-supported patient are presented including blood pressure assessment, medical therapy of the LVAD supported patient, and challenges related to anaesthesia and non-cardiac surgical interventions. Finally, important aspects to consider when discharging an LVAD patient home and palliative and end-of-life approaches are described., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The improvement in left ventricular assist device (LVAD) technology and scarcity of donor hearts have increased dramatically the population of the LVAD-supported patients and the probability of those patients to present to the emergency department with expected and non-expected device-related and patient-device interaction complications. The ageing of the LVAD-supported patients, mainly those supported with the 'destination therapy' indication, increases the risk for those patients to suffer from other co-morbidities common in the older population. In this second part of the trilogy on the management of LVAD-supported patients for the non-LVAD specialist healthcare provider, definitions and structured approach to the LVAD-supported patient presenting to the emergency department with bleeding, neurological event, pump thrombosis, chest pain, syncope, and other events are presented. The very challenging issue of declaring death in an LVAD-supported patient, as the circulation is artificially preserved by the device despite no other signs of life, is also discussed in detail., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The accepted use of left ventricular assist device (LVAD) technology as a good alternative for the treatment of patients with advanced heart failure together with the improved survival of patients on the device and the scarcity of donor hearts has significantly increased the population of LVAD supported patients. Device-related, and patient-device interaction complications impose a significant burden on the medical system exceeding the capacity of LVAD implanting centres. The probability of an LVAD supported patient presenting with medical emergency to a local ambulance team, emergency department medical team and internal or surgical wards in a non-LVAD implanting centre is increasing. The purpose of this paper is to supply the immediate tools needed by the non-LVAD specialized physician - ambulance clinicians, emergency ward physicians, general cardiologists, and internists - to comply with the medical needs of this fast-growing population of LVAD supported patients. The different issues discussed will follow the patient's pathway from the ambulance to the emergency department, and from the emergency department to the internal or surgical wards and eventually back to the general practitioner., (© 2021 European Society of Cardiology.)

Aims: To assess the short-term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single-centre cohort study of HTx recipients who received a two-dose SARS-CoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech)., Methods and Results: Whole blood for anti-spike IgG (S-IgG) antibodies was drawn at days 21-26 and at days 35-40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44-69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6-14) years. Only 15% of HTx recipients demonstrated the presence of positive S-IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54-229) AU/mL]. Overall, 49% of HTx recipients induced S-IgG antibodies in response to either the first or the full two-dose vaccine schedule [GMT 426 (IQR 106-884) AU/mL]. Older age [68 (IQR 59-70) years vs. 46 (IQR 34-63) years, P = 0.034] and anti-metabolite-based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non-responders to the first vaccine dose became S-IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S-IgG antibodies following SARS-CoV-2 two-dose vaccine., Conclusions: The generally achieved protection from SARS-CoV-2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied., (© 2021 European Society of Cardiology.)

While mortality of acute coronary syndrome (ACS) is known to have steadily decline over the last decades, data are lacking regarding the complex sub-population of patients with both coronary artery disease and cancer. A large single-center percutaneous coronary intervention (PCI) registry was used to retrieve patients who had a known diagnosis of malignancy during PCI. Patients were divided into two groups according to the period in which PCI was performed (period 1: 2006-2011, period 2: 2012-2017). Cox regression hazard models were implemented to compare primary endpoint, defined as the composite outcomes of major adverse cardiac events (MACE) (which include cardiovascular death, myocardial infarction or target vessel revascularization) and secondary endpoint of all-cause mortality, between the two time periods. A total of 3286 patients were included, 1819 (55%) had undergone PCI in period 1, and 1467 (45%) in period 2. Both short- and long-term MACE and overall mortality were significantly lower in patients who underwent PCI at the latter period (2.3% vs. 4.3%, p < 0.001 and 1.1% vs. 3.2%, p < 0.001 after 30 days and 24% vs. 30%, p < 0.001 and 12% vs. 22%, p < 0.001 after 2 years, respectively). However, in a multivariate analysis, going through PCI in the latter period was still associated with lower rates of overall mortality (HR 0.708, 95% confidence interval [CI] 0.53-0.93, p = 0.014) but there was no significant difference in MACE (HR 0.83, 95% CI 0.75-1.42, p = 0.16). Patients with cancer undergoing PCI during our most contemporary period had an improved overall survival, but no significant differences were observed in the composite cardiovascular endpoints, compared to an earlier PCI period. The management of coronary patients with cancer disease remains challenging., (© 2021. Springer Japan KK, part of Springer Nature.)

Aims: To compare the baseline cardiovascular characteristics of immunoglobulin light-chain (AL) and amyloid transthyretin (ATTR) cardiac amyloidosis (CA) and to investigate patients' contemporary cardiac outcomes., Methods: Single-center analysis of clinical, laboratory, echocardiographic and cardiac magnetic resonance imaging (CMRi) characteristics of AL and ATTR-CA patients' cohort (years 2013-2020)., Results: Included were 67 CA patients of whom 31 (46%) had AL-CA and 36 (54%) had ATTR-CA. Patients with ATTR-CA versus AL-CA were older (80 (IQR 70, 85) years versus 65 (IQR 60, 71) years, respectively, p<0.001) with male predominance (p = 0.038). Co-morbidities in ATTR-CA patients more frequently included diabetes mellitus (19% versus 3.0%, respectively, p = 0.060) and coronary artery disease (39% versus 10%, respectively, p = 0.010). By echocardiography, patients with ATTR-CA versus AL-CA had a trend to worse left ventricular (LV) ejection function (50 (IQR 40, 55)% versus 60 (IQR 45, 60)%, respectively, p = 0.051), yet comparable LV diastolic function. By CMRi, left atrial area (31 (IQR 27, 36)cm2 vs. 27 (IQR 23, 30)cm2, respectively, p = 0.015) and LV mass index (109 (IQR 96, 130)grams/m2 vs. 82 (IQR 72, 98)grams/m2, respectively, p = 0.011) were increased in patients with ATTR-CA versus AL-CA. Nevertheless, during follow-up (median 20 (IQR 10, 38) months), patients with AL-CA were more frequently admitted with heart failure exacerbations (HR 2.87 (95% CI 1.42, 5.81), p = 0.003) and demonstrated increased mortality (HR 2.51 (95%CI 1.19, 5.28), p = 0.015)., Conclusion: Despite the various similarities of AL-CA and ATTR-CA, these diseases have distinct baseline cardiovascular profiles and different heart failure course, thus merit tailored-cardiac management., Competing Interests: The authors have declared that no competing interests exist.

Aims: This study aimed to evaluate the different health-related quality of life (HR-QoL) aspects in patients with both short-term and long-term duration LVAD support at pre-specified time intervals., Methods and Results: We performed a single-centre HR-QoL analysis of short-term and long-term LVAD-supported patients using the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) and the Changes in Sexual Functioning Questionnaire along with a survey to evaluate patients' social and driving routines. Data were collected at baseline and at 6 or 12 month follow-up. Included were 46 patients with a median time from LVAD implantation of 1.1 [inter-quartile range (IQR) 0.5, 2.6] years. The median KCCQ-12 summary score was 56 (IQR 29, 74) with most favourable scores in the symptom frequency domain [75 (IQR 50, 92)] and worse scores in the physical limitation [42 (IQR 25, 75)] and QoL [44 (IQR 25, 75)] domains. No significant changes were apparent during study follow-up [KCCQ-12 summary score 56 (IQR 35, 80)], and no significant correlation between the KCCQ-12 summary score and ventricular assist device-support duration was detected (r = -0.036, P = 0.812). Sexual dysfunction was noted across all domains with a cumulative score of 31 (IQR 22, 42). Seventy-six per cent of patients resumed driving after LVAD implantation, and 43% of patients reported they socialize with family and friends more frequently since surgery., Conclusions: Short-term and long-term LVAD-supported patients had impaired HR-QoL and sexual function at baseline and at follow-up yet reported an improvement in social interactions and independency. A broader spectrum of patient's reported HR-QoL measures should be integrated into the pre-LVAD implantation assessment and preparation., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The optimal antithrombotic treatment for patients with atrial fibrillation (AF) that undergo percutaneous coronary intervention (PCI) is controversial. Dual therapy (clopidogrel and a direct oral anticoagulant [DOAC]) is safer than triple therapy (warfarin, aspirin, and clopidogrel), while efficacy is unclear. We aimed to evaluate thrombin generation (TG) under dual and triple therapy., Methods: A noninterventional prospective trial in patients with AF undergoing PCI. Patients received 4 weeks of triple therapy with aspirin, clopidogrel, and a DOAC followed by aspirin withdrawal. TG was measured in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) at 3 five to 21 points, day 1 after PCI (TIME 0), 4 weeks after PCI (TIME 1), and 2 weeks after aspirin withdrawal (TIME 2)., Results: Twenty-three patients (18 men, median age 78 years, 83% with acute coronary syndrome) were included. Endogenous thrombin potential (ETP) in PPP was high at TIME 0 compared with TIME 1 (ETP 3,178 ± 248 nM vs. 2,378 ± 222 nM, p = 0.005). These results remained consistent when measured in PRP. No significant difference in ETP was found before (TIME 1) and after aspirin withdrawal (TIME 2) although few patients had high ETP levels after stopping aspirin., Conclusions: TG potential is high immediately after PCI and decreases 4 weeks after PCI in patients receiving triple therapy. TG remains constant after aspirin withdrawal in most patients, suggesting that after 1 month the antithrombotic effect of dual therapy may be similar to triple therapy., (© 2021 S. Karger AG, Basel.)

Objective: This article describes the women population and work at a unique Women's Health Cardiology Clinic in order to raise cardiovascular disease awareness with an emphasis on women-specific risk factors, and thus to improve women's clinical outcomes. This expectantly will aid in opening similar centers allowing more women to get superior care., Methods: Electronic medical records of women referred to the Women's Health Cardiology Clinic were analyzed. The statistical analysis is descriptive in nature. Women's Health Cardiology Clinic personnel work as a multidisciplinary team, and patients receive specialized diagnostic tests and treatments. Referrals are by physicians according to traditional and women's specific risk factors for cardiovascular disease., Results: 985 women visited the Women's Health Cardiology Clinic, accumulating 2062 visits. Median age was 57.5 years. The majority of the women were menopausal (575 women, 58%), 62 pregnant with complications and 25 oncology patients. At least, 30% of women had diabetes/hypertension/or dyslipidemia. 72 women had a history of either cerebrovascular event or acute coronary syndrome, and 139 women had evidence of atherosclerosis. Overall, 388 women underwent endothelial function test, 40% of these women had a score indicating endothelial dysfunction. 277 women underwent a psychological intervention., Conclusion: Described here are the experiences from a multidisciplinary Women's Health Cardiology Clinic using a gender-specific cardiovascular care approach for women geared toward improved health and wellbeing. It is of utmost importance that this report will raise women-specific cardiovascular disease risk factors awareness in order to promote women's cardiovascular and overall health.

Background: We aimed to characterize patients with systemic amyloidosis stratified by a prior diagnosis of carpal tunnel syndrome (CTS) and to describe early echocardiographic parameters concomitant with CTS., Methods and Results: Patients with suspected amyloidosis during CTS diagnosis were excluded. Our cohort included 108 patients with systemic amyloidosis of which 36% had a prior CTS at a median of 4 years (interquartile range [IQR] 2.8-6.7 years) before disease diagnosis. Patients with prior CTS were more likely to present subsequently with cardiac amyloidosis (78% vs 53%, P = .013), yet overall survival was comparable between groups (53% vs 61%, P = .825). Prior CTS was more commonly diagnosed in subsequent patients with transthyretin (62%) than in patients with immunoglobulin light chain (24%, P < .001). Furthermore, in a subanalysis of patients subsequently diagnosed with cardiac amyloidosis, findings at CTS diagnosis (n = 17) demonstrated a mild increase in septal thickness 1.3 cm (IQR 1.2-1.5 cm), increased relative wall thickness 0.46 cm (IQR 0.45-0.58 cm), and increased left ventricular mass index 155 g/m 2 (IQR 92-177 g/m 2 ) compared with age-adjusted normal range echocardiographic values. Doppler mitral flow data was supportive of left ventricular diastolic dysfunction., Conclusions: Early echocardiographic findings at CTS diagnosis, preceding the diagnosis of cardiac amyloidosis by several years, are suggestive of increased wall thickness and diastolic dysfunction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Since the diagnosis of cardiac amyloidosis (CA) is often delayed, echocardiographic findings are frequently indicative of advanced cardiomyopathy. We aimed to describe early echocardiographic features in patients subsequently diagnosed with CA. Preamyloid diagnosis echocardiographic studies were screened for structural and functional parameters and stratified according to the pathogenetic subtype (immunoglobulin light-chain [AL] or amyloid transthyretin [ATTR]). Abnormalities were defined based on published guidelines. Our cohort included 75 CA patients of whom 42 (56%) were diagnosed with AL and 33 (44%) with ATTR. Forty-two patients had an earlier echocardiography exam available for review. Patients presented with increased wall thickness (1.3 [interquartile range {IQR} 1.0, 1.5] cm) ≥3 years before the diagnosis of CA and relative wall thickness was increased (0.47 [IQR 0.41, 0.50]) ≥7 years prediagnosis. One to 3 years before CA diagnosis restrictive left ventricular (LV) filling pattern was present in 19% of patients and LV ejection fraction ≤50% was present in 21% of patients. Right ventricular dysfunction was detected concomitantly with disease diagnosis. The echocardiographic phenotype of ATTR versus AL-CA showed increased relative wall thickness (0.74 [IQR 0.62, 0.92] versus 0.62 [IQR 0.54, 0.76], p = 0.004) and LV mass index (144 [IQR 129, 191] versus 115 [IQR 105, 146] g/m 2 , p = 0.020) and reduced LV ejection fraction (50 [IQR 44, 58] versus (60 [IQR 53, 60]%, p = 0.009) throughout the time course of CA progression, albeit survival time was similar. In conclusion, increased wall thickness and diastolic dysfunction in CA develop over a time course of several years and can be diagnosed in their earlier stages by standard echocardiography., (Copyright © 2020 Elsevier Inc. All rights reserved.)