The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence ...for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT).
In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.
After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval CI, 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29).
In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).
The aim of this study was to evaluate left ventricular global longitudinal strain (LVGLS), N-terminal pro brain natriuretic peptide (Nt-ProBNP), and Troponin T as non-invasive markers for acute ...cellular rejection (ACR) diagnosis and severity assessment after heart transplantation (HTx).
We retrospectively included all HTx patients transplanted from 2013 to 2019. At each visit, the patients were subjected to endomyocardial biopsy (EMB), measurement of Nt-ProBNP and Troponin T, and protocoled echocardiography with assessment of LVGLS. Sudden drop in graft function (SDGF) was defined as a drop in LVGLS ≥-2% in combination with either an increase in Troponin T ≥20% or Nt-ProBNP ≥30% compared with levels at the latest visit.
We included 1,436 EMBs from 83 HTx patients. The biopsies were grouped as 0R (n = 857), 1R (n = 538), and ≥2R (n = 41). LVGLS was lower and Troponin T and Nt-ProBNP higher in the 2R group than in the 0R and 1R groups (LVGLS: -12.9 ± 3.8% versus -16.9 ± 3.1% and -16.1 ± 3.3%; Troponin T: 79 33;230 ng/l versus 27 13;77 ng/l and 27 14;68 ng/l; Nt-ProBNP: 4,174 1,095;9,510 ng/l versus 734 309;2,210 ng/l and 725 305;2,082, all p < 0.01). A SDGF was seen at 45 visits of which 19 had ≥2R ACR. EMBs showed ACR in 20 cases without SDGF. Finally, neither was SDGF seen nor did the EMB show rejection in 1,136 cases. Thus, the sensitivity of SDGF for ≥2R ACR detection was 49% (32-65) and specificity 98% (97-99). The positive predictive value (PPV) was 42% (31-55) and the negative predictive value (NPV) 98% (98-99). The diagnostic value improved in a sub-analysis excluding EMBs within 3 months after HTx, clinically interpreted false positive ≥2R ACR cases, and cases with ≥2R ACR who recently (<2 weeks) were treated with intravenous methylprednisolone due to ≥2R ACR (sensitivity 75% (48-93), specificity 97% (96-98), NPV 99% (99-100), and PPV 39% (27-52).
Patients with ≥2R ACR have lower LVGLS and higher Troponin T and Nt-ProBNP than patients without 2R rejection. A non-invasive model combining changes in LVGLS and Troponin T or Nt-ProBNP showed excellent negative predictive value and moderate sensitivity and may be used as a gatekeeper to invasive biopsies after HTx.
The DanGer Shock trial test the hypothesis that left ventricular (LV) mechanical circulatory support with Impella CP transvalvular microaxial flow pump improves survival in patients with ST segment ...elevation acute myocardial infarction complicated by cardiogenic shock (AMICS) compared to conventional guideline-driven treatment. This paper describes the rationale and design of the randomized trial, in addition to the baseline characteristics of the population screened and enrolled so far.
The DanGer Shock study is a prospective, multicenter, open-label trial in patients with AMICS randomized 1:1 to Impella CP or current guideline-driven therapy with planned enrollment of 360 patients. Patients comatose after out of hospital cardiac arrest are excluded. Eligible patients are randomized immediately following shock diagnosis. Among patients randomized to receive Impella CP, the device is placed prior to angioplasty. The primary endpoint is all-cause mortality at 180 days. Baseline characteristics of patients screened and randomized in the DanGer Shock as of June 2018 are compared with 2 contemporary AMICS studies.
As of end of June 2018, 314 patients were screened and 100 patients were randomized. Patients had median arterial lactate of 5.5 mmol/L (interquartile range 3.7-8.8 mmol/L), median systolic blood pressure of 76 mmHg (interquartile range 70-88 mmHg), and median LV ejection fraction of 20% (interquartile range 10%-30%).
The DanGer Shock trial will be the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. Baseline characteristics of the first 100 randomized patients indicate a population in profound cardiogenic shock.
Abstract Objectives The aims of this study were to characterize cardiac allograft vasculopathy (CAV) phenotypes using optical coherence tomography (OCT) and to evaluate the prognostic significance of ...OCT-determined CAV severity. Background Intravascular OCT enables in vivo characterization of CAV microstructure after heart transplantation. Methods Sixty-two patients undergoing heart transplantation were enrolled at routine angiography from September 2013 through October 2015 and prospectively followed until censoring on May 27, 2016. Optical coherence tomographic acquisitions aimed for the longest possible pull-backs, including proximal segments of all 3 major vessels. Plaques and bright spots were analyzed by delineating circumferential borders and measuring the angulation of total circumference. Layers were contoured for absolute and relative estimates. Nonfatal CAV progression (NFCP) during follow-up was registered. NFCP included occluded vessels or severe (≥70%) new angiographic coronary stenosis or percutaneous coronary intervention. Results A total of 172 vessels were categorized as follows: no CAV, n = 111; mild to moderate CAV (<70% stenosis), n = 40; and severe CAV (≥70% stenosis), n = 21. Layered fibrotic plaque (LFP) was the most prevalent plaque component, and the extent increased with angiographic CAV severity (p < 0.01). During follow-up, 22 of 172 vessels (13%) experienced NFCP. Median follow-up was 633 days (interquartile range: 432 to 808 days). The extent of LFP (hazard ratio: 5.0; 95% confidence interval: 2.1 to 12.4; p < 0.0001) and the extent of bright spots (hazard ratio: 6.2; 95% confidence interval: 2.4 to 15.8, p < 0.001) were strong predictors of NFCP. By combining LFP and bright spots, a strong NFCP predictive model was obtained (hazard ratio: 8.9; 95% confidence interval: 2.6 to 29.9; p < 0.0001). Conclusions OCT enables the detection of CAV-associated plaque compositions and allows early detection and differentiation of vessel wall disease not visible on angiography. LFP was the most prevalent plaque component, was strongly associated with NFCP, and may be associated with stepwise CAV progression caused by organizing mural thrombi. (The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients; NCT02077764 )
Diagnosing and monitoring acute cellular rejection (ACR) is a major objective in the surveillance of heart-transplanted patients. The aim of this study was to evaluate the value of global ...longitudinal strain (GLS), measured by two-dimensional speckle-tracking echocardiography, as a noninvasive tool for graft function monitoring in relation to ACR.
The study population consisted of all heart-transplanted patients who underwent biopsy and corresponding echocardiography at one institution from 2011 to 2013 (n = 64). ACR was classified according to the International Society of Heart and Lung Transplantation (0R-3R). Changes in graft function were serially evaluated before, during, and in the resolving period after ACR.
No sign of rejection was seen in 268 biopsies (52.7%), minimal rejection (1R) in 202 biopsies (39.7%), and moderate rejection (2R) in 39 biopsies (7.7%); no patients had severe (3R) rejection. A significant difference in GLS was observed comparing the groups with 0R (-15.5%; 95% confidence interval, -16.2% to -14.2%), 1R (-15.3%; 95% confidence interval, -16.0% to -14.6%), and 2R (-13.8%; 95% confidence interval, -14.6% to -12.9%) rejection (P < .0001). GLS remained significantly reduced in the 2R group despite the exclusion of patients with impaired systolic function (ejection fraction < 50%), allograft vasculopathy, and late rejection (>2 years) after transplantation. In the serial assessment, GLS was decreasing significantly at the time of moderate 2R rejection and improved significantly in the resolving period. The traditional diastolic Doppler parameters, E-wave deceleration time and isovolumetric relaxation time, were unaffected by rejections, whereas the E/A and E/e' ratios were significantly higher in the 2R group (P = .004 and P = .01) compared with the 0R and 1R groups.
GLS is significantly reduced during moderate (2R) ACR and improves significantly in the resolving period. The present results provide encouraging evidence to consider the routine use of GLS as a marker of graft function involvement during ACR.
Acute mixed cellular and antibody-mediated rejection (MR) has an estimated prevalence of 7.8%. However, knowledge of MR immune pathogenesis in cardiac graft rejection remains sparse. We report a case ...of acute MR in a heart transplant patient with a mutation in the MYH7 gene encoding the protein β-myosin heavy chain, resulting in familial hypertrophic cardiomyopathy. The patient presented with substantial eosinophilic infiltration and extensive production of Human Leukocyte Antigen (HLA)-antibodies associated with shared epitopes. Eosinophilic infiltration in the endo- and myocardium was diagnosed in routine post-transplant biopsies stained with hematoxylin-eosin on day 6 after transplantation. On day 27, the patient presented with dyspnea, weight gain, increased pro-brain natriuretic peptide, and was hospitalized due to suspected acute rejection. Endomyocardial biopsies showed eosinophils in endo- and myocardium with additional lymphocytes and hyperplastic endothelium. Immunohistochemistry, including CD31/CD68 double stain confirmed endothelium-associated macrophages in capillaries and severe C4d positivity in the capillaries and endocardial endothelium. Lymphocytes were identified as primarily CD45+/CD3+ T cells with a concomitant few CD45+/CD20+ B cells. HLA-antibody analysis demonstrated a significant increase in 13 HLA-antibodies present in pre-transplant-serum, of which anti-B7 was donor-specific, and 23 strong
de-novo
HLA-class I antibodies of which anti-B62 was donor-specific. 72% of HLA-antibodies, including the two donor-specific antibodies, shared the same HLA antigen epitope; 43P+69A or 163L+167W. This is a case reporting both HLA-antibody and pathohistological data indicating the need for better understanding of interactions between cellular and antibody-mediated immune response mechanisms in graft rejection, and the significance of pre-transplant donor-specific antibodies during immunological pre-transplant risk assessment.
Most studies on vocational rehabilitation after heart transplantation (HTX) are based on self-reported data. Danish registries include weekly longitudinal information on all public transfer payments. ...We intended to describe 20-year trends in employment status for the Danish heart-transplant recipients, and examine the influence of multimorbidity and socioeconomic position (SEP). Linking registry and Scandiatransplant data (1994-2018), we conducted a study in recipients of working age (19-63 years). The cohort contained 492 recipients (79% males) and the median (IQR) age was 52 years (43-57 years). Five years after HTX, 30% of the survived recipients participated on the labor market; 9% were in a flexible job with reduced health-related working capacity. Moreover, 60% were retired and 10% eligible for labor market participation were unemployed. Recipients with multimorbidity had a higher age and a lower prevalence of employment. Five years after HTX, characteristics of recipients with labor market participation were: living alone (27%) versus cohabitation (73%); low (36%) versus medium-high (64%) educational level; low (13%) or medium-high (87%) income group. Heart-transplant recipients with multimorbidity have a higher age and a lower prevalence of employment. Socioeconomically disadvantaged recipients had a lower prevalence of labor market participation, despite being younger compared with the socioeconomically advantaged.
Abstract
Background
Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory ...out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome.
Methods
This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan–Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality.
Results
A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients
.
Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18–1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03–1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12–1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52–0.76).
Conclusions
A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.
This dual-site study evaluated the diagnostic accuracy of the method.
Pittsburgh compound (11CPIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for ...the diagnosis of cardiac amyloidosis (CA).
The study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain AL and 21 transthyretin ATTR amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min-1) were applied prospectively.
The diagnostic accuracy of visual inspection of 11CPIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative 11CPIB uptake discriminated CA from controls with a 94% (95% confidence interval CI: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. 11CPIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as 11CPIB PET positive.
In a dual-center setting, 11CPIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were 11CPIB PET positive, indicating that the method may detect early stages of CA.
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Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance ...thoracic transplant patients, but robust, long-term data are required.
In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization.
Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24.
Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.
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