Systolic Heart Failure is Associated with Higher Mortality Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Nationwide Analysis.

Heart failure (HF) is prevalent among patients with aortic stenosis and presents a poor prognosis. In order to better portray outcomes for HF patients undergoing transcatheter aortic valve replacement (TAVR), we evaluated clinical outcomes in patients with systolic vs diastolic heart failure who underwent TAVR in a large nationwide database. We searched the National Inpatient Sample (NIS) for hospitalized adult patients who underwent TAVR with coexisting history of systolic (SHF) or diastolic heart failure (DHF) as a secondary diagnosis using the ICD-10 codes. The primary outcome was in-hospital mortality, with secondary outcomes of cardiac arrest (CA), cardiogenic shock (CS), respiratory failure (RF), Non-ST elevation myocardial infarction (NSTEMI), acute kidney injury (AKI), use of cardiac and respiratory assist device, and health care utilization defined as length of stay, average hospital cost (AHC) and patient charge (APC). Both univariate and multivariate logistic, generalized linear, and Poisson regression analyses were used to evaluate and test the outcomes. A P-value of <0.05 was significant. A total of 106,815 patients were admitted to acute care hospitals for TAVR, and 73% had a secondary diagnosis of heart failure (41% had SHF and 59% DHF). SHF group were older (mean age of 78.9 years [SD ± 8.9] vs 79.9 years [SD ± 8.3]) with more males (61.8% vs 48.2%) and white predominant (whites [85.9% vs 87.9%]). Compared to DHF, SHF had higher inpatient mortality (1.75% vs 1.14%, P = 0.003), CA (1.31% vs 0.81%, P = 0.01), NSTEMI (2.52% vs 1.0%, P = 0.001), RF (10.87% vs 8.01%, P = 0.001), and CS (3.94% vs 1.14%, P = 0.001). In addition, SHF had greater LOS (5.1 days vs. .3.9, P = 0.0001) & AHC ($52,901 vs $48,070, P = 0.0001). HF is common among patients admitted for TAVR. SHF had worse CV outcomes, greater use of hospital resources, and higher acute care hospital mortality compared to those with DHF.

Incidence, predictors and outcomes of new onset systolic heart failure following orthotopic liver transplant: A systematic review.

BACKGROUND: New onset Systolic heart failure (SHF), characterized by new onset left ventricular (LV) systolic dysfunction with a reduction in ejection fraction (EF) of <40%, is a common cause of morbidity and mortality among Orthotopic liver transplant (OLT) recipients. Therefore, we aimed to evaluate the prevalence, the pre-transplant predictors, and the prognostic impact of SHF post-OLT. METHODS: We conducted a systematic review of the literature using electronic databases MEDLINE, Web of Science, and Embase for studies reporting acute systolic heart failure post-liver transplant from inception to August 2021. RESULT: Of 2604 studies, 13 met the inclusion criteria and were included in the final systematic review. The incidence of new-onset SHF post OLT ranged from 1.2% to 14%. Race, sex, or body mass index did not significantly impact the post-OLT SHF incidence. Alcoholic liver cirrhosis, pre-transplant systolic or diastolic dysfunction, troponin, brain natriuretic peptide (BNP), blood urea nitrogen (BUN) elevation, and hyponatremia were noted to be significantly associated with the development of SHF post-OLT. The significance of MELD score in the development of post-OLT SHF is controversial. Pre-transplant beta-blocker and post-transplant tacrolimus use were associated with a lower risk of developing SHF. The average 1-year mortality rate in patients with SHF post-OLT ranged from 0.00% to 35.2%. CONCLUSION: Despite low incidence, SHF post-OLT can lead to higher mortality. Further studies are required to fully understand the underlying mechanism and risk factors.

Efficacy of Implantable Cardioverter Defibrillator in Nonischemic Systolic Heart Failure According to Sex: Extended Follow-Up Study of the DANISH Trial.

BACKGROUND: Men and women may respond differently to certain therapies for heart failure with reduced ejection fraction, including implantable cardioverter defibrillators (ICD). In an extended follow-up study of the DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality), adding 4 years of additional follow-up, we examined the effect of ICD implantation according to sex. METHODS: In the DANISH trial, 1116 patients with nonischemic systolic heart failure were randomized to receive an ICD (N=556) or usual clinical care (N=550). The primary outcome was all-cause mortality. RESULTS: Of the 1116 patients randomized in the DANISH trial, 307 (27.5%) were women. During a median follow-up of 9.5 years, women had a lower associated rate of all-cause mortality (hazard ratio [HR], 0.60 [95% CI, 0.47-0.78]) cardiovascular death (HR, 0.62 [95% CI, 0.46-0.84]), nonsudden cardiovascular death (HR, 0.59 [95% CI, 0.42-0.85]), and a numerically lower rate of sudden cardiovascular death (HR, 0.70 [95% CI, 0.40-1.25]), compared with men. Compared with usual clinical care, ICD implantation did not reduce the rate of all-cause mortality, irrespective of sex (men, HR, 0.85 [95% CI, 0.69-1.06]; women, HR, 0.98 [95% CI, 0.64-1.50]; Pinteraction=0.51). In addition, sex did not modify the effect of ICD implantation on sudden cardiovascular death (men, HR, 0.57 [95% CI, 0.36-0.92]; women, HR, 0.68 [95% CI, 0.26-1.77]; Pinteraction=0.76). CONCLUSIONS: In patients with nonischemic systolic heart failure, ICD implantation did not provide an overall survival benefit, but reduced sudden cardiovascular death, irrespective of sex. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00542945.

Effect of implantable cardioverter-defibrillators in patients with non-ischaemic systolic heart failure and concurrent coronary atherosclerosis.

AIMS: Prophylactic implantable cardioverter-defibrillators (ICD) reduce mortality in patients with ischaemic heart failure (HF), whereas the effect of ICD in patients with non-ischaemic HF is less clear. We aimed to investigate the association between concomitant coronary atherosclerosis and mortality in patients with non-ischaemic HF and the effect of ICD implantation in these patients. METHODS AND RESULTS: Patients were included from DANISH (Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators in Patients with Non-Ischaemic Systolic Heart Failure on Mortality), randomizing patients to ICD or control. Study inclusion criteria for HF were left ventricular ejection fraction ≤ 35% and increased levels (>200 pg/mL) of N-terminal pro-brain natriuretic peptide. Of the 1116 patients from DANISH, 838 (75%) patients had available data from coronary angiogram and were included in this subgroup analysis. We used Cox regression to assess the relationship between coronary atherosclerosis and mortality and the effect of ICD implantation. Of the included patients, 266 (32%) had coronary atherosclerosis. Of these, 216 (81%) had atherosclerosis without significant stenoses, and 50 (19%) had significant stenosis. Patients with atherosclerosis were significantly older {67 [interquartile range (IQR) 61-73] vs. 61 [IQR 54-68] years; P < 0.0001}, and more were men (77% vs. 70%; P = 0.03). During a median follow-up of 64.3 months (IQR 47-82), 174 (21%) of the patients died. The effect of ICD on all-cause mortality was not modified by coronary atherosclerosis [hazard ratio (HR) 0.94; 0.58-1.52; P = 0.79 vs. HR 0.82; 0.56-1.20; P = 0.30], P for interaction = 0.67. In univariable analysis, coronary atherosclerosis was a significant predictor of all-cause mortality [HR, 1.41; 95% confidence interval (CI), 1.04-1.91; P = 0.03]. However, this association disappeared when adjusting for cardiovascular risk factors (age, gender, diabetes, hypertension, smoking, and estimated glomerular filtration rate) (HR 1.05, 0.76-1.45, P = 0.76). CONCLUSIONS: In patients with non-ischaemic systolic heart failure, ICD implantation did not reduce all-cause mortality in patients either with or without concomitant coronary atherosclerosis. The concomitant presence of coronary atherosclerosis was associated with increased mortality. However, this association was explained by other risk factors.

O-ring-induced transverse aortic constriction (OTAC) is a new simple method to develop cardiac hypertrophy and heart failure in mice.

Suture-based transverse aortic constriction (TAC) in mice is one of the most frequently used experimental models for cardiac pressure overload-induced heart failure. However, the incidence of heart failure in the conventional TAC depends on the operator's skill. To optimize and simplify this method, we proposed O-ring-induced transverse aortic constriction (OTAC) in mice. C57BL/6J mice were subjected to OTAC, in which an o-ring was applied to the transverse aorta (between the brachiocephalic artery and the left common carotid artery) and tied with a triple knot. We used different inner diameters of o-rings were 0.50 and 0.45 mm. Pressure overload by OTAC promoted left ventricular (LV) hypertrophy. OTAC also increased lung weight, indicating severe pulmonary congestion. Echocardiographic findings revealed that both OTAC groups developed LV hypertrophy within one week after the procedure and gradually reduced LV fractional shortening. In addition, significant elevations in gene expression related to heart failure, LV hypertrophy, and LV fibrosis were observed in the LV of OTAC mice. We demonstrated the OTAC method, which is a simple and effective cardiac pressure overload method in mice. This method will efficiently help us understand heart failure (HF) mechanisms with reduced LV ejection fraction (HFrEF) and cardiac hypertrophy.

Retrospective Study of 573 Patients with Heart Failure Evaluated for Coronary Artery Disease at Toulouse University Center, France.

BACKGROUND Heart failure (HF) most commonly occurs due to ischemic heart disease from stenotic coronary artery disease (CAD). HF is classified into 3 groups based on the percentage of the ejection fraction (EF): reduced (HFrEF), mid-range (HFmrEF), and preserved (HFpEF). This retrospective study included 573 patients who presented with HF based on the evaluation of EF and were evaluated for CAD by coronary angiography before undergoing coronary angioplasty at a single center in Toulouse, France. MATERIAL AND METHODS This retrospective observational study included patients recently diagnosed with HF or acute decompensation of chronic HF and referred for coronary angiography at Toulouse University Hospital between January 2019 and May 2020. RESULTS Significant CAD was found in 55.8%, 55%, and 55% of the whole population, HFpEF, and HFrEF groups, respectively. Older age, male sex, and diabetes mellitus were the main risk factors for ischemic HF. Except for age and sex, patients with ischemic HFpEF were comparable to those with non-ischemic HFpEF, unlike the ischemic HFrEF group, which had more common cardiovascular risk factors than the non-ischemic HFrEF group. The ischemic HFpEF group had an older age and higher rate of dyslipidemia than the ischemic HFrEF group. CONCLUSIONS At our center, CAD was diagnosed in more than half of patients who presented with heart failure with preserved or reduced EF. Older age and male sex were the common risk factors in patients with HFpEF and HFrEF.

Neutrophil degranulation biomarkers characterize restrictive echocardiographic pattern with diastolic dysfunction in patients with diabetes.

OBJECTIVE: To investigate the potential association between neutrophil degranulation and patterns of myocardial dysfunction in a cohort of patients with type 2 diabetes mellitus (T2DM). BACKGROUND: Two distinct phenotypes of diabetic cardiomyopathy have been described: a restrictive phenotype with diastolic dysfunction (restrictive/DD) and a dilative phenotype with systolic dysfunction (dilative/SD). However, the underlying determinants of these two patterns are not yet recognized. METHODS: In this single-centre, observational, cross-sectional study, 492 patients were recruited. Ultrasonographic measurements were performed by two experienced sonographers, blinded to the clinical data of the participants. Serum biomarkers of neutrophil degranulation were measured by enzyme-linked immunosorbent sandwich assay (ELISA). RESULTS: After adjustment for confounders, resistin, myeloperoxidase, matrix metalloproteinase 8 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 complex were positively associated with the restrictive/DD pattern compared with the normal pattern. Similarly, MPO was positively associated with the dilative/SD pattern compared with the normal pattern, and resistin was negatively associated with the dilative/SD pattern compared with the restrictive/DD pattern. CONCLUSIONS: Neutrophil degranulation is associated with the restrictive/DD echocardiographic pattern in patients with T2DM, but not with the normal pattern and dilative/SD patterns. Neutrophils could have a pivotal role in the pathogenesis of myocardial dysfunction, and particularly diastolic dysfunction, in patients with T2DM.

Comparação entre classificação funcional e fração de ejeção em pacientes com insuficiência cardíaca na Doença de Chagas / Functional classification versus ejection fraction in patients with heart failure and Chagas Disease

Introdução: A doença de Chagas é uma infecção causada pelo protozoário Trypanosoma cruzi. É considerada um importante problema de saúde do mundo, tendo como manifestações a dilatação cardíaca, arritmias e morte. A insuficiência cardíaca é uma síndrome complexa e de elevada morbimortalidade, que evolui com complicações semelhantes. Para categorizar a gravidade da insuficiência cardíaca, utilizamos a classificação funcional da New York Heart Association, para estratificar risco e terapias para cardiopatias. Além disso, a reduzida fração de ejeção do ventrículo esquerdo, medida pelo ecocardiograma, tem relação direta com mau prognóstico. Objetivo: Comparar a relação entre a classificação funcional pela New York Heart Association e a medida da fração de ejeção do ventrículo esquerdo em pacientes ambulatoriais chagásicos e não chagásicos. Metódos: Estudo de corte transversal na coorte, composto de pacientes acompanhados em ambulatório de insuficiência cardíaca. Foram realizadas avaliação de prontuários, entrevista clínica e verificação da classificação funcional e da fração de ejeção do ventrículo esquerdo pelo ecocardiograma. Os dados foram arquivados em banco de dados e analisados pelo Statistical Package for the Social Sciences. Resultados: No período de agosto de 2018 a julho de 2019, foram selecionados 127 indivíduos com insuficiência cardíaca. Destes, 34 (26,8%) eram portadores da doença de Chagas e 93 (73,3%) eram não Chagas. Observou-se predominância do sexo masculino (53,5%) e de idade >60 anos (61,4%). Houve predomínio da classe funcional II nos grupos. Em relação à fração de ejeção dos pacientes chagásicos e não chagas, observou-se que, respectivamente, 71% contra 93% dos pacientes tinham fração de ejeção reduzida, 21% versus 6% tinham fração de ejeção intermediária e 8% versus 1% fração de ejeção preservada. Conclusão: Houve associação entre classe funcional avançada e reduzida fração de ejeção do ventrículo esquerdo principalmente em chagásicos, podendo ser usada para acompanhamento evolutivo ambulatorial. (AU)

Introduction: Chagas disease, an infection caused by the protozoan Trypanosoma cruzi, is an important health problem worldwide that causes cardiac dilation, arrhythmias, and death. Heart failure is a complex syndrome with high morbidity and mortality rates that progresses with similar complications. The New York Heart Association functional classification is used to categorize heart failure severity and stratify heart disease risks and therapies. A reduced left ventricular ejection fraction measured by echocardiography is directly related to a poor prognosis. Objective: To compare the relationship between New York Heart Association functional classification and left ventricular ejection fraction in Chagas versus no Chagas disease outpatients. Methods: Cross-sectional study in a cohort of patients followed at a heart failure clinic. Medical records, clinical interviews, functional classification, and left ventricular ejection fraction by echocardiography were analyzed. The data were filed in a database and analyzed using SPSS software. Results: A total of 127 patients with heart failure were selected from August 2018 to July 2019. Of them, 34 (26.8%) had Chagas disease and 93 (73.3%) had no Chagas disease. There was a predominance of men (53.5%) and patients aged > 60 years (61.4%). There was also a predominance of functional class II. Of the Chagas and no Chagas disease patients, 71% versus 93% had a reduced ejection fraction, 21% versus 6% had a mid-range ejection fraction, and 8% versus 1% had a preserved ejection fraction, respectively. Conclusion: There was an association between advanced functional class and reduced left ventricular ejection fraction, especially in Chagas patients, information that can be used for outpatient follow-up. (AU)

Synergistic prognostication of left ventricular hypertrophy and three-dimensional mechanical dyssynchrony in heart failure.

AIMS: In this study, we investigated the prognostic interplay of left ventricular hypertrophy and mechanical dyssynchrony (LVMD), both of which can be measured three-dimensionally by gated myocardial perfusion imaging (MPI), in patients with chronic systolic heart failure (HF). METHODS AND RESULTS: In 829 consecutive HF patients with reduced left ventricular ejection fraction less than 50%, LVMD was evaluated as a standard deviation (phase SD) of regional onset of mechanical contraction phase angles. A phase histogram was created by Fourier phase analysis applied to regional time-activity curves obtained by gated MPI. Left ventricular mass index (LVMI) was measured by Corridor 4DM version 6.0. Patients were followed up with a primary endpoint of lethal cardiac events (CE) for a mean interval of 34 months. CE were documented in 223 (27%) of the HF patients. The CE group had a greater phase SD and a greater LVMI than those in the non-CE group. Patients in the CE group had a more advanced age, greater New York Heart Association (NYHA) functional class, left ventricular cavity size, and left atrial diameter or septal E/e' and lower kidney or cardiac function than did patients in the non-CE group. Phase SD > 37 and LVMI > 122.7 g/m2 were identified as optimal cut-off values by receiver operating characteristic analyses for discrimination of the most increased risk HF subgroup from others (P < 0.0001). When classified into four patient subgroups using both cut-off values, HF patients with phase SD > 37 (LVMD) and LVMI > 122.7g/m2 had the highest CE rate among the subgroups (P < 0.0001). Univariate analysis and subsequent multivariate analysis with a Cox proportional hazards model showed that phase SD and LVMI were significant independent predictors of CE with hazard ratios of 1.038 (confidence interval [CI], 1.024-1.051, P < 0.0001) and 1.005 (CI, 1.001-1.008, P = 0.0073), respectively, as well as conventional clinical parameters such as age, NYHA class, estimated glomerular filtration rate (eGFR), and BNP concentration. Patients with increased phase SD and LVMI had incrementally improved prognostic values of clinical parameters including age, NYHA functional class, eGFR, and BNP with increases in the global χ2 value: 5.9 for age; 139.5 for age and NYHA; 157.9 for age, NYHA, and eGFR; 163.9 for age, NYHA, eGFR, and BNP; 183.4 for age, NYHA, eGFR, BNP, and phase SD; and 192.5 for age, NYHA, eGFR, BNP, phase SD, and LVMI. CONCLUSIONS: Three-dimensionally assessed LVMD has independent prognostic values and can improve the risk stratification of chronic HF patients synergistically in combination with conventional clinical parameters.

Ratio of Early Mitral Inflow Velocity to the Global Diastolic Strain Rate and Global Left Ventricular Longitudinal Systolic Strain Predict Overall Mortality and Major Adverse Cardiovascular Events in Hemodialysis Patients.

BACKGROUND: The ratio of early mitral inflow velocity to the global diastolic strain rate (E/E'sr) and global longitudinal systolic strain (GLS) of the left ventricle (LV) are emerging indices of diastolic and systolic functions, respectively, for the LV. Their prognostic significance in the prediction of mortality and cardiovascular (CV) outcomes remains underexplored in hemodialysis (HD) patients. METHODS: This prospective study included 190 maintenance HD patients. The E/E'sr ratio and GLS were assessed using two-dimensional speckle tracking echocardiography. The clinical outcomes included overall mortality, CV mortality, and major adverse cardiovascular events (MACE). The associations between the E/E'sr ratio, GLS, and clinical outcomes were evaluated using multivariate Cox regression analysis. The incremental values of the E/E'sr ratio and GLS in outcome prediction were assessed by χ 2 changes in Cox models. RESULTS: Over a median follow-up period of 3.7 years, there were 35 overall deaths, 16 CV deaths, and 45 MACE. Impaired diastolic function with a higher E/E'sr ratio was associated with overall mortality (HR, 1.484; 95% CI, 1.201-1.834; p < 0.001), CV mortality (HR, 1.584; 95% CI, 1.058-2.371; p = 0.025), and MACE (HR, 1.205; 95% CI, 1.040-1.397; p = 0.013) in multivariate adjusted Cox analysis. Worsening GLS was associated with overall mortality (HR, 1.276; 95% CI, 1.101-1.480; p = 0.001), CV mortality (HR, 1.513; 95% CI, 1.088-2.104; p = 0.014), and MACE (HR, 1.214; 95% CI, 1.103-1.337; p < 0.001). The E/E'sr ratio and GLS had better outcome prediction than the E to early diastolic mitral annular velocity (E/E') ratio and left ventricular ejection fraction (LVEF). Moreover, adding the E/E'sr ratio and GLS to Cox models containing relevant clinical and conventional echocardiographic parameters improved the prediction of overall mortality (p < 0.001), CV mortality (p < 0.001), and MACE (p < 0.001). CONCLUSION: The E/E'sr ratio and GLS, as emerging indices of LV diastolic and systolic functions, significantly predict mortality and CV outcomes and outperform conventional echocardiographic parameters in outcome prediction in HD patients.

The effect of implantable cardioverter-defibrillator in patients with diabetes and non-ischaemic systolic heart failure.

AIMS: Implantable cardioverter-defibrillator (ICD) implantation reduce the risk of sudden cardiac death, but not all-cause death in patients with non-ischaemic systolic heart failure (HF). Whether co-existence of diabetes affects ICD treatment effects is unclear. METHODS AND RESULTS: We examined the effect of ICD implantation on risk of all-cause death, cardiovascular death, and sudden cardiac death (SCD) according to diabetes status at baseline in the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischaemic Systolic Heart Failure on Mortality (DANISH) trial. Outcomes were analysed by use of cumulative incidence curves and Cox regressions models. Of the 1116 patients enrolled, 211 (19%) had diabetes at baseline. Patients with diabetes were more obese, had worse kidney function and more were in New York Heart Association Class III/IV. The risk of device infections and other complications in the ICD group was similar among patients with and without diabetes (6.1% vs. 4.6% P = 0.54). Irrespective of treatment group, diabetes was associated with higher risk of all-cause death, cardiovascular death, and SCD. The treatment effect of ICD in patients with diabetes vs. patients without diabetes was hazard ratio (HR) = 0.92 (0.57-1.50) vs. HR = 0.85 (0.63-1.13); Pinteraction = 0.60 for all-cause mortality, HR = 0.99 (0.58-1.70) vs. HR = 0.70 (0.48-1.01); Pinteraction = 0.25 for cardiovascular death, and HR = 0.81 (0.35-1.88) vs. HR = 0.40 (0.22-0.76); Pinteraction = 0.16 for sudden cardiac death. CONCLUSION: Among patients with non-ischaemic systolic HF, diabetes was associated with higher incidence of all-cause mortality, primarily driven by cardiovascular mortality including SCD. Treatment effect of ICD therapy was not significantly modified by diabetes which might be due to lack of power.

Predictors of Systolic Heart Failure and Mortality Following Orthotopic Liver Transplantation: a Single-Center Cohort.

OBJECTIVES: The purpose of this study was to identify risk factors that may predict heart failure with reduced ejection fraction (HFrEF) following orthotopic liver transplantation (OLT) and associated mortality. BACKGROUND: HFrEF following OLT is a poorly understood phenomenon, reported in 3% to 7% of transplanted patients. METHODS: This is a retrospective analysis of 176 consecutive patients who underwent OLT from 2010 to 2017. Multivariate logistic regression was used to identify associations between cardiovascular risk factors and perioperative variables with post-OLT HFrEF, defined as reduction in left ventricular ejection fraction of at least 10% and left ventricular ejection fraction less than or equal to 40% with acute heart failure symptoms. Multivariate cox proportional hazards regression (with inverse probability weighting by propensity scores) was used to evaluate effects of HFrEF on 1-year mortality. RESULTS: Of the176 patients, 14% developed HFrEF with a median of 5 days. History of heart failure (OR 10.99, 2.15-56.09; P = .04) and intraoperative transfusion of greater than 11 units of packed red blood cells (OR 3.377, 1.025-11.13; P = .045) were associated with increased incidence of HFrEF. Pre-transplant hemoglobin greater than 8.5 g/dL (OR 0.252, CI 0.0954- 0.665; P = .05) was protective against HFrEF. Thirty-three percent of HFrEF group died within 1 year (HR 7.36, 2.57-21.12; P < .001). CONCLUSIONS: The incidence of acute HFrEF post-OLT is 14% and is associated with a 7-fold increase in 1-year mortality. Cirrhotic cardiomyopathy and stress-induced cardiomyopathy maybe the underlying mechanisms. Our study identified risk factors associated with post-OLT HFrEF and should provide additional guidance for risk stratification of patients undergoing OLT.

Comprehensive cardiac phenotyping in large animals: comparison of pressure-volume analysis and cardiac magnetic resonance imaging in pig post-myocardial infarction systolic heart failure.

Large animal ischemic cardiomyopathy models are widely used for preclinical testing of promising novel therapeutic approaches. Pressure volume (PV) loop analysis and cardiac magnetic resonance imaging (CMRI) allow functional and morphological phenotyping. In this study we performed a comparative analysis of both methods highlighting the strength of each and their synergistic potential. Myocardial infarction (MI) was created in German farm pigs (German Landrace) by 2 h LCX occlusion (n = 11) and subsequent reperfusion. Cardiac function was assessed by PV-loops and CMRI 56 and 112 days post-MI. Two hours occlusion of the LCX led to mid-size left ventricular (LV) MI represented by high-sensitive troponin T (hsTnT) 3 days post-MI, correlating well with cardiac CMRI late enhancement. CMRI determined end-diastolic and end-systolic volumes significantly increased post-MI, while ejection fraction was reduced in infarcted animals compared to the sham group (n = 6). PV-loop derived preload-insensitive parameters of systolic and diastolic function were diminished post-MI compared to sham animals while preload-dependent parameters only deteriorated in advanced HF. PV-loop analysis significantly correlates with CMRI analysis of cardiac function in pig post-MI ischemic cardiomyopathy. PV-Loop analysis accurately quantifies LV volumetry and function in post-MI HF, and thus eccentric LV morphology. PV-loop analysis correlates well to cardiac MRI. Preload-insensitive parameters show high sensitivity to quantify HF while preload-sensitive parameters are not able to quantify early-stages of LV HF.

Is mild asymptomatic left ventricular systolic dysfunction always predictive of adverse events in high-risk populations? Insights from the DAVID-Berg study.

BACKGROUND: Mild asymptomatic left ventricular systolic dysfunction (ALVSD) may be associated with incident heart failure (HF). However, this gray zone group needs incremental risk refinement. We hypothesized that diastolic dysfunction (DD) may refine HF and death risk prediction in mild ALVSD. METHODS AND RESULTS: Among 4047 subjects aged ≥55/≤80 years followed by 10 general practitioners in northern Italy, the DAVID-Berg study prospectively enrolled 623 asymptomatic outpatients at increased risk for HF. Baseline evaluation included clinical visit, N-terminal pro B-type natriuretic peptide, and echocardiogram. Based on left ventricular ejection fraction (LVEF) and DD, subjects were classified as: control group (normal LVEF, n = 459, 76%), mild ALVSD (LVEF ≥40%/<53%) without DD (n = 89, 15%) and with DD (n = 54, 9%). Subjects with LVEF <40% or without full echocardiographic data were excluded from the analysis (n = 21). Mean age of the population was 69 ±7 years, 56% were men, mostly hypertensive, mean LVEF was 61%. During a median follow-up of 5.7 years, 88 subjects (15%) experienced HF/death events (59 HF events and 29 deaths). Compared to the control group, mild ALVSD was associated with a higher risk of incident HF/death (hazard ratio 1.80, 95% confidence interval 1.10-2.93, adjusted P = 0.019) according to the Cox proportional hazards model. However, this higher risk was present only in subjects with combined DD (P = 0.005) and not in those without it (P = 0.30). Results were consistent even considering the individual components of the primary outcome. CONCLUSION: In a high-risk population, an echocardiographic exam is normally performed to assess systolic dysfunction. Our data underline the importance of also relying on DD to risk stratify mild ALVSD. Mild ALVSD might be a predictor of adverse events mainly in subjects with combined DD, though further studies are needed to confirm these results.

Accuracy of cardiac magnetic resonance imaging to rule out significant coronary artery disease in patients with systolic heart failure of unknown aetiology: Single-centre experience and comprehensive meta-analysis.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of systolic heart failure (HF). Cardiac magnetic resonance imaging (CMR) is a non-invasive technique that detects a myocardial infarction scar as subendocardial or transmural late gadolinium enhancement (st-LGE). AIM: We sought to evaluate whether a lack of st-LGE could rule out CAD in new-onset systolic HF of unknown aetiology. METHODS: We included 232 consecutive patients with new-onset HF and left ventricular ejection fraction ≤35% who underwent both coronary angiography and CMR to assess HF aetiology. CAD was defined as the presence of coronary artery stenosis≥50% on a coronary angiogram. We assessed sensitivity, specificity, and positive and negative likelihood ratios (PLR and NLR) of the presence of st-LGE to detect underlying CAD. A complementary meta-analysis of 11 studies (including ours) was also performed. RESULTS: In our study, 49 (21.1%) patients had CAD. The sensitivity and specificity of the presence of st-LGE to detect CAD were 69 and 92%, respectively. PLR and NLR were 8.47 and 0.33, respectively. In the meta-analysis, 1227 patients were included, and the prevalence of CAD ranged from 19.2 to 68.3%. Sensitivity, specificity, PLR and NLR were 87% (95% confidence interval [CI] 0.80-0.92), 93% (95% CI 0.89-0.96), 12.91 (95% CI 7.70-21.64) and 0.14 (95% CI 0.09-0.22), respectively. Altogether, 55 patients presented CAD with no st-LGE; inversely, 75 patients presented st-LGE with no CAD. CONCLUSION: With a CMR specificity of 93%, the absence of st-LGE rules out significant underlying CAD in patients with systolic HF of unknown aetiology in most cases.