bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal values for indexed left atrial end-systolic volume by two- and three-dimensional echocardiography. A cross-sectional population study
Authors: Eriksen-Volnes T , Nes B , Wislof U , Lovstakken L , Dalen H
Published: October 2021

Background

The left atrium volume and function gives important prognostic and diagnostic information. Normal values for left atrial end-systolic volume index (LASVI) is derived from 4-chamber and 2-chamber views or three-dimensional (3D) imaging. In current recommendations LASVI above 34 ml/m2 has been regarded dilated when assessing diastolic function and left ventricular filling pressures. It is not known if improved image quality by new scanners or more dedicated atrial focused views provide the same normal reference ranges.

Material and methods

We examined a large sub-population participating in a population based health study by high-end echocardiographic scanners. LA volume was assessed at end-systole in two-dimensional (2D) recordings focusing on the left atrium to avoid foreshortening. Additionally, 3D full volume recordings were acquired stitching 2–4 cardiac cycles when feasible using breath hold. All echocardiograms were analyzed offline using dedicated commercial software with manual tracing of the endocardial border and calculation of volume by the summation of discs method in 2D recordings.

Results

2462 of 5763 invited persons was examined by echocardiography. 1048 persons were excluded due to known heart disease, atrial fibrillation, antihypertensive treatment, diabetes mellitus or findings of clear pathology on echocardiography leaving 1414 persons presumed free of cardiovascular disease or major risk factors for the analyses.

Mean ± SD age was 57.9±12.4, and 55.8% was females. Mean (SD) LASVI in females and males were 27.6±9.7 ml/m2 and 30.7±11.1 ml/m2 by 2D imaging, respectively. Similarly, mean ± SD LASVI in females and males were 29.1±6.8 ml/m2 and 30.5±7.9 ml/m2 by 3D. The distribution of LASVI by age is showed in figure 1. The mean ± SD difference between 2D and 3D intra-individual measurements were 0.31±9.0 ml/m2 corresponding to 1.1%. By 2D assessment 24.1% of this presumed healthy cohort had a LASVI over 34 ml/m2, with more males than females had enlarged left atria by this definition (32.7% vs 20.1%, p<0.001).

Conclusion

New reference ranges for left atrial size is provided for 2D and 3D recordings. By dedicated 2D recordings normal values are larger than previously recorded, and the difference between 2D and 3D recordings are less than previously reported.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): NTNU and the HUNT study Figure 1. Indexed left atrial end-systolic volume, summation of discs method using adjusted left atrial view vs age. The red line denotes 34 ml/m2 used as the cut-off value in present guidelines.
Right ventricular dysfunction is a predictor of non-response to cardiac resynchronization therapy
Authors: Neves Pereira M , Leite P.V.H , Dias G , Cardoso A.F , Tinoco M , Azevedo O , Lourenco M , Ribeiro S , Ferreira F , Sanfins V , Lourenco A
Published: October 2021

Introduction

Cardiac resynchronization therapy (CRT) has been of great benefit to many heart failure (HF) patients with reduced ejection fraction (EF) and intraventricular conduction delay. However, approximately 30% of patients fail to respond to CRT. We investigated baseline characteristics that might influence response to CRT.

Methods

We retrospectively enrolled 227 patients undergoing CRT implantation between 2013 and 2020 according to the guidelines. 118 patients were included in our analysis, from whom all data were available. Clinical, electrocardiographic and echocardiographic parameters were evaluated at baseline and 6 months after CRT implantation. Response to CRT was defined as an increase in left ventricular ejection fraction (LVEF) >10%. Right ventricular systolic dysfunction (RVSD) was defined as S' velocity <9.5 cm/s or tricuspid anular plane systolic excursion (TAPSE) <17 mm. Chronic kidney disease (CKD) was defined as GFR <60 ml/min/1.73m2.

Results

118 patients were included (mean age 69±11 years, 66.1% males, 39.8% ischemic etiology; 35,6% atrial fibrillation, baseline LVEF 27,6±6%). After 6 months of CRT, 65 patients (55.1%) were considered responders. Responders were more frequently female than non responders (43,1% vs 22,6, p=0.02). Atrial fibrillation and CKD were more prevalent in non responders (47,2% vs 26,2%, p=0.018; 62,3% vs 21,5%, p<0.001, respectively). RVSD was present in 60,4% of non responders vs 16,9% of responders (p<0.001). In responder group, the mean S' velocity was 10,9±2,1 cm/s vs 9,1±2,1 cm/s in non responder group, p<0.001. The mean TAPSE was also higher in responder group (20,3±7,2 mm vs 16,5±4,4 mm, p=0.031). On multivariate analysis only RVSD (OR 7,754; 95% CI 2,968 – 20,282 p<0.001] and CKD (OR 5,434; 95% CI 2,109 – 14,002; p<0.001) were independently associated with non-response to CRT.

Conclusion

From a range of preoperative characteristics, multivariate analysis only identified RVSD and CKD as independent predictors of CRT response, with S' <9,5 cm/s and TAPSE <17 mm associated with non-response to CRT. This study highlights the importance of routine RV assessment in order to improve patient selection and optimize CRT response in heat failure patients.

Funding Acknowledgement

Type of funding sources: None.
Impact of kidney disease on left ventricular assisted device outcomes: insight from National Readmission Database
Authors: Shatla I , Abumoawad A , Cheng A.-L , Lopez Candales A
Published: October 2021

Introduction

Improvements in device technology, appropriate patient selection and timing of left ventricular assist device (LVAD) implantation have allowed this technique as the preferred destination therapy for advanced end-stage heart failure (HF) patients whom are not candidates for heart transplantation. Unfortunately, up to a third of these patients still experience poor outcomes following LVAD implantation. Although some clinical factors have been identified as potential risk factors for these poor outcomes, there is paucity of data regarding the impact of baseline kidney disease following LVAD implantation.

Methods

We used the Nationwide Readmission Database (NRD), identifying patients who underwent implantable LVAD placement 2010–2017 using ICD-9 and 10 codes. Patients were stratified into 3 mutually exclusive groups based on presence and severity of chronic kidney disease (CKD) during the LVAD placement hospitalization: non-CKD, CKD and end stage renal disease requiring dialysis (CKD-D). Outcomes were all-cause and cause-specific 30-day readmissions as well as 90-day readmission.

Result

Within 30 days after discharge 28.5% of patients were readmitted. Of those without CKD, 27.8% were readmitted, compared to 29% of those with CKD and 31% of those with CKD-D. Compared to non-CKD (adjusted for demographics, index hospitalization and chronic comorbidity factors, and year), odds of 30-day readmission were 1.542 [95% CI 1.028–2.313] times higher for those with CKD-D, whereas those with CKD had similar 30-day readmission risk (OR 1.074 [95% CI 0.951–1.213]). Those with CKD and CKD-D had higher risk of 30-day readmission for acute (HF), bleeding and transfusion need.

Within 90 days after discharge 48.88% of patients were readmitted. Of those without CKD, 46.2% were readmitted, compared to 50%of those with CKD and 45% of those with CKD-D. Odds of 90-day readmission were 1.203 (95% CI 1.088–1.330) times higher for those with CKD than non-CKD group, Also those with CKD-D requiring dialysis had higher 90-day readmission risk (OR 1.287 [95% CI 0.954–1.736]) when compared to non-CKD. Those with CKD had higher risk of 90-day readmission for acute (HF), gastrointestinal bleeding and arrhythmia while those with CKD-D had higher risk of 90-day readmission for DVT and anemia. There was no difference in 30-day and 90-day readmission between all groups for stroke, device related thrombosis or infection.

Conclusion

It appears, based on our analysis, that although having CKD does not confer additional risk for either 30 or 90-days readmissions; these post LVAD patients have a greater risk of acute HF exacerbation, bleeding and arrhythmias. We believe that these results are very important and should be included into future risk models when deciding on LVAD implantation.

Funding Acknowledgement

Type of funding sources: None.
Intermittent therapy with levosimendan in patients with advanced heart failure
Authors: Blaschke M , Kiwi A , Hagl C , Weis M
Published: October 2021

Introduction

Therapeutic options for patients with advanced heart failure on the high-urgent (HU) heart transplant (HTx) waiting list are limited. In view of the limited data on the usefulness of classic inotropes, the calcium sensitizer levosimendan (Lev) may be a possible alternative for patients in need of a repetitive therapy with an inotropic agent as a bridge to HTx.

Method

In a single-center open-label study we retrospectively analyzed data from 34 HU-listed patients (from a total collective of 95 HU patients) who repetitively received Lev (12.5 mg; 0,05–0.1 μg/kg/min over 24–48h) in 2–8 weeks intervals due to cardiac instability and/or progressive second organ dysfunction. Potential side effects as well as changes of kidney, liver and heart functional parameters were evaluated (0–6 days before, 4–8 days and 14–20 days after Lev infusion).

Patient collective: age 51±10 years, 6 women, 28 men; NYHA stage III-IV.

11 Patients with ischemic cardiomyopathy (32%), 19 patients with dilated cardiomyopathy (56%), 4 patients with arrhythmogenic right ventricular cardiomyopathy (12%).

Results

The waiting time for HTx was up to 12 months (6±5 months). There were no adverse, serious events (resuscitation, defibrillation for ventricular tachycardia (VT), intubation and ventilation, renal replacement therapy) up to 7 days after Lev infusion. Transient cardiac arrhythmias (ventricular bursts or non-sustained VTs) occurred in 11 patients (32%) with spontaneous termination and no need of urgent anti-arrhythmic therapy.

The values for sodium, potassium, Hb and CRP did not change significantly after Lev. In contrast, there was a significant reduction in creatinine after 4–8 days (initially 1.43±0.4 mg/dl; after 4–8 days 1.28±0.3; p<0.0005) with an increase again after 14–20 days (1.43±0.3 mg/dl).

The bilirubin value was significantly reduced after 4–8 days (initially 1.63±0.7 mg/dl; after 4–8 days 1.30±0.5; p<0.0005) with only partial (non-significant) increases again over the course (1.34±0.5 mg/dl). The BNP value was significantly reduced 4–8 days after administration of Lev (initially 1565±1136 ng/l; after 4–8 days 1103±895; p<0.0001) and increased again in the longer time course (1462±1001 ng/l; p<0.001 versus 4–8 days).

28 patients were successfully transplanted (82%). 6 patients remained without HTx (18%), of which 1 patient (3%) with clinical improvement could be discharged. 2 patients (6%) received an LVAD and 3 patients (9%) died during the waiting period.

Conclusion

Intermittent therapy with Lev as “a bridge to transplant” is safe and effective concerning deterioration of heart failure and prevention of progressive kidney/hepatic dysfunction. However, a prospective randomized multi-center trial is necessary to underscore the encouraging data of this observational, single center study.

Funding Acknowledgement

Type of funding sources: None.
Lipid profile in cardiac transplantation: a closer look at bad cholesterol
Authors: Alyaydin E , Pogoda C.A , Pistulli R , Lange S.A , Welp H , Dell Aquila A , Sindermann J , Reinecke H , Tuleta I
Published: October 2021

Background

When it comes to lipid-lowering therapy, the primary goal is still to reduce the low-density lipoprotein levels. Although remnant cholesterol (RC), including predominantly intermediate- and very-low-density lipoproteins, is a known cardiovascular risk factor, reliable reference values, as well as therapy strategies, are yet to be validated. Additionally, the role of RC after heart transplantation is still unclear.

Aim

To assess the clinical and prognostic relevance of lipid profile and, in particular, of remnant cholesterol in very long-term follow-up after HTx.

Methods

We performed a retrospective analysis of the clinical and laboratory parameters collected at last follow-up in an outpatient setting. Additionally, remnant cholesterol levels were estimated using the formula (in mg/dL): remnant cholesterol = total cholesterol – (HLD-C + LDL-C).

Results

Out of 174 patients with a mean age of 45.2±15.0 years at the time of HTx and a mean follow-up of 13.1±6.5 years, 142 (81.6%) were on statin treatment. Mean cholesterol level was borderline high (184.1±48.4 mg/dL), whereas mean LDL and triglyceride values were markedly elevated (103.6±39.2 and 161.8±83.8 mg/dL, respectively). HDL results were found to be 57.1±17.5 mg/dL. Statin treatment was associated with significantly lower LDL levels (124.6±53.5 vs. 98.8±33.6 mg/dL on statins, p=0.013), but failed to show prognostic relevance in a univariate cox-regression analysis (HR 0.79, 95% CI 0.37 – 1.72, p=0.57). RC was elevated in comparison to the background population with a mean level of 23.5±17.3 mg/dL (24.2±18.1 in male and 21.3±14.8 mg/dL in female) and a tendency for lower values when on treatment with statins but without statistical significance (28.5±19.2 vs. 22.3±16.8 mg/dL on statins, p=0.07). Treatment with higher doses of statins showed no relevant influence on the RC levels (p=0.62). Additionally, elevated RC was associated with higher C-reactive protein values as a sign of systemic inflammation (CRP >0.5 mg/dL, OR 1.1, 95% CI 1.007 – 1.046, p=0.007). In a multivariate cox-regression analysis (adjusted for total cholesterol, LDL and triglycerides) RC was identified as a significant factor influencing mortality (HR 1.11, 95% CI 1.05 – 1.17, p<0.001).

Conclusions

When addressing dyslipidaemia in heart transplantation, statin therapy can help reduce LDL levels, but this approach seems to be insufficient in achieving clinical benefit. Remnant cholesterol is a factor, which has proinflammatory properties and can potentially influence the prognosis in HTx. The possible therapeutic alternatives for this overseen component of the lipid profile are yet to be elucidated.

Funding Acknowledgement

Type of funding sources: None.
Early follow-up in the cardiological day hospital after heart surgery. Impact on hospital readmissions and emergency room visits
Authors: Vaqueriza Cubillo D , Gomez Mariscal E , Dominguez Munoa M , Beltran Herrera C , Suberviola Sanchez-Caballero V , Cano Moracho J.M , Giganto Arroyo M.L , Mora Yague L , Jimenez Loeches S , Sarrion Catala M.M , Cortina Camarero C , Cortes Beringola A , Gonzalez Pinto A , Cuerpo Caballero G , Munoz Aguilera R
Published: October 2021

Introduction

In the first few months after heart surgery, readmissions and emergency visits are common. In order to reduce these events, we developed an early follow-up protocol after discharge based on attention in our cardiological day hospital (CDH), which allows clinical and analytical assessment, monitoring and intravenous treatment at successive visits. The objective of the study is to assess the effectiveness of the protocol after its implementation.

Methods

Patients in our area discharged after heart surgery between 2013 and 2017 were included. They were divided into two groups, one with conventional follow-up and one with initial follow-up in CDH. Baseline clinical characteristics, type of surgery and surgical risk were compared. The primary endpoint was the time to the first readmission or emergency visit. The follow-up time was 200 days from discharge. Quantitative variables were compared using Student's t test and categorical variables using chi-square test. Cox proportional hazards model was used for multivariate analysis.

Results

321 patients, 160 with conventional and 161 with CDH follow-up, were included. There were no differences in baseline characteristics (age, type of surgery, comorbidities, risk and hospital stay) except for sex (44.7% women in conventional group vs 33.8% in HDC, p=0.04). The results of readmissions and the composite endpoint (readmission or emergency visit) at 30, 90 and 200 days are shown in the table. We found a trend of decreasing events in the CDH group, although statistical significance was not achieved. In multivariate analysis, the variables independently associated (p<0.05) with an increase in the combined endpoint at 200 days were: female sex, prior atrial fibrillation, hypertension and an Euroscore surgical risk index greater than 3. The time to a first cardiological assessment after discharge decreased significantly in the CDH group (58 vs 18 days, p<0.001).

Conclusions

In patients followed in CDH after heart surgery, there is a trend towards less readmissions and emergency visits in the first six months after discharge. Some baseline characteristics have been shown to be independently associated with the risk of events, which will help us to identify the most at-risk patients, on which an intervention could have a greater magnitude of benefit.

Funding Acknowledgement

Type of funding sources: None. Table 1. ResultsFigure 1. Hazard of composite end-point
The relationship of dehydration and body mass index with the occurrence of atrial fibrillation in heart failure patients
Authors: Chuda A , Kaszkowiak M , Banach M , Maciejewski M , Bielecka-Dabrowa A
Published: October 2021

Background/Introduction

Heart failure (HF) and atrial fibrillation (AF) are two conditions that are likely to dominate the next years of cardiovascular (CV) care. These diseases frequently coexist and they can beget one another due to similar risk factors and similar pathophysiology.

Purpose

The aim of the study was to assess the relationship of dehydration, body mass index (BMI) and other indices with the occurrence of AF in HF patients.

Methods

The study included 113 patients [median age 64 years; 57.52% male] hospitalized due to HF. Baseline demographics, body mass analysis, echocardiographic results, key cardiopulmonary exercise test (CPET) parameters, six minute walk distance (6MWD) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score were assessed.

Results

Of all patients, 23 (20.35%) had AF, and 90 (79.65%) had sinus rhythm (SR). Patients with AF were older (med. 66 vs 64 years; p=0.039), with higher BMI (32.02 vs. 28.51 kg/m2; p=0.017) and percentage of fat content (37.0 vs. 27.9%, p=0.014). They were more dehydrated, with a lower percentage of total body water (TBW%) (45.7 vs 50.0%; p=0.022). Clinically, patients with AF had more often higher New York Heart Association (NYHA) class (III vs II; p<0.001), shorter 6MWD (median 292.35 vs 378.4 m; p=0.001) and a lower KCCQ overall summary score (52.60 vs 73.96 points; p=0.002). Patients with AF had significantly lower exercise capacity as measured by peak oxygen consumption (peak VO2) (0.92 vs 1.26 mL/min, p=0.016), peak VO2/kg (11 vs. 15 mL/kg/min; p<0.001), and percentage of predicted VO2max (pp-peak VO2) (62.5 vs 70.0; p=0.010). We also found VE/VCO2 (med.33.85 vs 32.20; p=0.049) to be higher and peak oxygen pulse (8.5 vs 11 mL/beat; p=0.038) to be lower in patients with AF than in patients without AF. In a multiple logistic regression model higher BMI (OR 1.23 per unit increase, p<0.001) and higher left atrial volume index (LAVI) (OR 1.07 per unit increase, p=0.03), lower tricuspid annular plane systolic excursion (TAPSE) (OR 0.74 per unit increase, p=0.03) and lower TBW% in body mass analysis (OR 0.90 per unit increase, p=0.03) were independently related to AF in patients with HF.

Conclusions

Increased volume of left atrium and right ventricular systolic dysfunction are well-known predictors of AF occurrence in patients with HF, but hydration status and increased body mass also seem to be important factors of AF in HF patients.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Impact of idiopathic pulmonary fibrosis on the clinical outcomes of patients admitted for acute decompensated heart failure: an analysis of U.S national inpatient sample
Authors: Almani M , Usman M , Qudrat Ullah M , Yousuf M , Fatima N
Published: October 2021

Background

The cardiovascular manifestations of idiopathic pulmonary fibrosis (IPF) include heart failure, pulmonary hypertension, coronary artery disease, cardiac arrhythmias and cardiac manifestations of drugs used to treat IPF. Cardiac disease can be worsened by hypoxia and pulmonary hypertension by IPF. The impact of IPF on the outcomes of acute decompensated heart failure (ADHF) is not well studied.

Purpose

We aim to determine the outcomes of patients admitted for ADHF with co-morbid IPF.

Methods

Data were extracted from the National Inpatient Sample (NIS) 2016 - 2018 Database. The NIS was searched for hospitalizations for adult patients with ADHF as principal discharge diagnosis with and without IPF as secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality. Secondary outcomes are detailed in table 1. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. A univariate screen was done to further confirm that these factors affected outcomes with variables having a p-value less than 0.2 included in the multivariate regression analysis. STATA software was used to for analysis.

Results

Of 1,007,824 patients admitted for ADHF, 1850 (0.2%) had IPF. Patients with IPF were significantly younger at the time of hospitalization for ADHF (71 years vs. 76 years, p<0.001). There were 46% females in IPF group compared to 48% in the non-IPF group, p=0.451. The adjusted odds ratio (aOR) for inpatient mortality for ADHF with IPF compared to those without IPF was 2.82 (95% CI 1.897–4.215, p<0.001). Patients with comorbid IPF had 1 day increase in mean length of stay (95% CI 0.475–1.525, p<0.001). Detailed outcomes are listed in table 1.

Conclusions

Co-morbid IPF leads to higher inpatient mortality and higher length of hospitalization in patients with acute decompensated heart failure. It is prudent to risk stratify these patients to improve overall morbidity and mortality.

Funding Acknowledgement

Type of funding sources: None.
Acute heart failure in women: phenotypes and outcomes in Mexico. Gender differences?
Authors: Alvarez-San Gabriel A , Gonzalez-Pacheco H , Arias-Mendoza A , Guizar-Sanchez C , Manzur-Sandoval D , Araiza-Garaygordobil D , Jordan-Rios A , Gopar-Nieto R , Sierra-Lara Martinez D , Mendez-Ortiz A , Briseno-De La Cruz J L , Favela-Garcia K , Sanchez A , Ramirez-Rangel P
Published: October 2021

Background

Latin America has limited information about sex differences in acute heart failure and about hospital outcome. This study sought to examine clinical features and outcomes of patients with AHF in a coronary care unit of a single Mexican institution.

Aims

To examine the sex differences in clinical features, phenotype, etiologies and mortality of patients with acute heart failure in a single institution of Latin-America.

Methods

This was a retrospective study of consecutive patients hospitalized with AHF in a coronary care unit of a Mexican teaching hospital between January 2006 and December 2020.

Results

During the study period, 24,262 patients were hospitalized, 9,408 (38.8%) had AHF, of which 3,230 (34.3%) were women. Women with AHF, compared to men with AHF, were older (median, 64 vs. 61 years, P<0.0001) and more likely to have a history of hypertension, stroke, atrial fibrillation, and hypothyroidism. The ischemic heart disease was more frequent in men (67.8% vs 40.5%; p<0.0001), however, valvular heart disease and cardiomyopathies were more frequent in women (32.9% vs 16.9% and 16.0 vs 10.2%, respectively; p<0.0001) (figure 1).

At presentation, women had a higher frequency of worsening chronic HF (59.8%), worse NYHA class, preserved left ventricular ejection fraction (LVEF) (median, 45% vs 38%; P<0.0001), and lower estimated glomerular filtration rates.

Overall, unadjusted in-hospital mortality was higher in women (18.9 vs 16.1, p<0.0001), but only different in ischemic heart disease (18.2 vs 15.7, p<0.03) and valvular heart disease (21.8 vs 18.2%, p<0.03). In-hospital mortality adjusted for age and LVEF showed that women had a higher risk of death. (Odds ratio 1.34; 95% CI, 1.19–1.51, P<0.0001) (figure 2).

Conclusions

In this cohort of Mexican patients hospitalized with AHF, there were important differences in clinical characteristics and aetiologies between women and men. Women have a higher frequency of worsening chronic HF and as well as renal function. Nevertheless, despite having a preserved LVEF, in-hospital mortality was higher in women compared to men.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Aetiology in acute heart failureFigure 2. Kaplan-Meier curves for mortality
Right heart dysfunction and readmission risk across left ventricular ejection fraction status in patients with acute heart failure
Authors: Santas Olmeda E , Minana G , Palau P , De La Espriella R , Lorenzo M , Nunez G , Heredia R , Chorro F J , Nunez J
Published: October 2021

Background

Right heart dysfunction (RHD) parameters, such as right ventricular to pulmonary artery uncoupling or significant tricuspid regurgitation (TR) are increasingly important in heart failure (HF), especially in patients with preserved ejection fraction. In this study, we aimed to evaluate the association of advanced RHD with the risk of recurrent admissions across the spectrum of left ventricular ejection fraction (LVEF).

Methods

We included 3,383 consecutive patients discharged for acute HF (AHF). Of them, in 1,435 (42.4%) pulmonary artery systolic pressure (PASP) could not be accurately measured, leaving a final sample size of 1,948 patients. Advanced RHD was defined as the combination of a ratio of tricuspid annular plane systolic excursion (TAPSE)/PASP<0.36 and a significant functional TR (n=196, 10.2%). Negative binomial regression analyses were used to evaluate the risk of recurrent admissions.

Results

At a median follow up of 2.2 years (IQR=0.63–4.71), 3,782 readmissions were registered in 1,296 patients (66.5%). Patients with advanced RHD showed higher rates of readmissions, but only if LVEF≥40% (p<0.001). In multivariable analyses, this differential association persisted for CV and HF recurrent admissions (p-value for interaction=0.016 and p=0.020; respectively). Advanced RHD was independently associated with the risk of recurrent CV and HF admissions if HF with LVEF≥40% (IRR: 1.99, 95% CI: 1.47–2.69, p<0.001; and IRR: 2.02, 95% CI: 1.45–2.81, p<0.001; respectively). In contrast, it was not associated with readmission risks if LVEF<40%.

Conclusion

Following an admission for AHF, advanced RHD was strongly associated with a higher risk of recurrent CV and HF admissions, but only in patients with LVEF≥40%.

Funding Acknowledgement

Type of funding sources: None.
Impact of cardiac amyloidosis on outcomes of patients hospitalized with heart failure in Germany
Authors: Goebel S , Hobohm L , Desuki A , Gori T , Muenzel T , Rapezzi C , Wenzel P , Keller K
Published: October 2021

Background

Amyloidosis is a multi-systemic disease resulting from deposition of misfolded proteins as insoluble fibrils in the interstitium of affected organs including the heart, subsequently leading to organ failure. Cardiac involvement is predominantly observed in light chain (AL) amyloidosis and wild-type transthyretin (ATTRwt) amyloidosis.

Purpose

We aimed to investigate prevalence and prognostic implications of cardiac amyloidosis of any etiology on outcomes of hospitalized patients with heart failure (HF) in Germany.

Methods

We analyzed data of the German nationwide inpatient sample (2005–2018) of patients hospitalized for HF (including myocarditis with HF and heart transplantation with HF). HF patients with amyloidosis (defined as cardiac amyloidosis [CA]) were compared with those HF patients without amyloidosis and impact of CA on outcomes was assessed (source: Research Data Center (RDC) of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005–2018, and own calculations).

Results

During this fourteen-year observational period 5,478,835 hospitalizations of HF patients were analyzed. Amyloidosis was coded in 5,407 hospitalizations of HF patients (0.1%). Prevalence of CA was 1.87 hospitalizations per 100,000 German population. CA patients were younger (75.0 [IQR 67.0/80.0] vs. 79.0 [72.0–85.0] years, p<0.001), predominantly male (68.9%) and had a higher prevalence of cancer (14.8% vs. 3.6%, P<0.001) compared with HF without amyloidosis. Although patients without amyloidosis had a pronounced cardiovascular risk profile -especially arterial hypertension (45.4% vs. 35.6%; p<0.001) and diabetes mellitus (38.9% vs. 18.5%; p<0.001)- and a higher prevalence of concomitant coronary artery disease (40.5% vs. 34.5%; p<0.001) and chronic obstructive pulmonary disease (17.1% vs. 9.4%; p<0.001), adverse in-hospital events including necessity of transfusions of blood constituents (7.1% vs. 5.4%, p<0.001) and cardio-pulmonary resuscitation (CPR, 2.7% vs. 1.4%; p<0.001) were more frequent in CA. CA was independently associated with acute kidney failure (OR 1.40 [95% CI 1.28–1.52], p<0.001), CPR (OR 1.58 [95% CI 1.34–1.86], p<0.001), intracerebral bleeding (OR 3.13 [95% CI 1.68–5.83], p<0.001) and in-hospital mortality in the 6th and 8th decade of life (6thdecade: OR 1.40 [95% CI 1.01–1.94], p=0.042; 8thdecade: OR 1.18 [95% CI 1.03–1.35], p=0.02).

Conclusions

CA was identified as an independent risk factor for complications and in-hospital mortality in HF patients. Physicians should be aware of this issue concerning treatments and monitoring of CA-patients.

Funding Acknowledgement

Type of funding sources: None.
Both short-and long-term treatment with the direct AMP kinase activator PXL770 improves cardiac function in ZSF-1 rats
Authors: Stephan Y , Souille M , Larcheveque M , Gluais-Dagorn P , Hallakou-Bozec S , Nicol L , Mulder P
Published: October 2021

Introduction

AMPK is a central energy sensor with cardioprotective effects, and its activation has emerged as a target for the treatment of metabolic syndrome-related cardiac dysfunction. PXL770 is the first direct AMPK activator under clinical development, currently investigated for the treatment of NASH. Since potential cardiac benefits of PXL770 have not been previously assessed we investigated whether short- and long-term PXL770 treatment exerts protective cardiac effects in rats with metabolic syndrome.

Methods

ZSF-1 rats were treated with PXL770 (150 mg/kg orally BID for 90 days initiated at the age of 12 weeks, or for 7 days initiated at the age of 23 weeks) in order to determine left ventricular (LV) function and remodeling.

Results

After 90 days, untreated ZSF-1 rats showed signs of LV diastolic dysfunction, illustrated by the increase in LV end-diastolic pressure (LV EDP; 5.58±0.57 and 8.28±1.02 mmHg in lean and ZSF-1 rats, respectively; p<0.05) and in LV end-diastolic pressure volume-relation (LV EDPVR; 1.10±0.23 and 5.44±0.65 mmHg/RVU in lean and ZSF-1 rats, respectively; p<0.05) with preserved LV systolic function, illustrated by the slight decrease in LV fractional shortening (LV FS; 46±1 and 42±1% in lean and ZSF-1 rats, respectively; p<0.05) and similar LV end-systolic pressure (LV ESP; 173±10 and 197±6 mmHg, respectively) or LV end-systolic pressure volume-relation (LV ESPVR; 32.7±4.2 to 28.6±1.4 mmHg/RVU, respectively). LV diastolic dysfunction was associated with a significant increase in LV tissue collagen density (2.62±0.17 and 4.03±0.13%, respectively) without an alteration in LV weight (1.27±0.02 to 1.22±0.03 g; respectively)

Short- and long-term treatment with PXL770 improved LV diastolic function in treated ZSF-1, illustrated by the reduced LV EDP (5.34±0.93 and 5.98±0.94 mmHg, short- and long-term PXL770, respectively) and the reduced LV EDPVR (3.31±0.43 and 2.73±0.16 mmHg/RVU, respectively; p<0.05 vs untreated ZSF-1). Simultaneously LV FS was significantly increased (52±1 and 50±1%, respectively; p<0.05 vs untreated ZSF-1), as well as LV ESPVR (34.6±1.4 and 33.0±0.9 mmHg/RVU, respectively; p<0.05 vs untreated ZSF-1). The improvement of diastolic function was associated with a reduction in LV weight (1.19±0.04 and 1.17±0.02 g, respectively; long-term PXL770 p<0.0.5 vs untreated ZSF-1) and a significant reduction in collagen density after long-term PXL770 (3.35±0.12%; p<0.05) but not short-term PXL770 (4.22±0.30%).

Conclusion

These results suggest that PXL770 exerts protective effects on cardiac function and structure in developing or established cardiomyopathy. Thus, by directly activating AMPK, the PXL770 appears promising for the treatment of cardiac dysfunction associated with metabolic diseases.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Poxel SA
Impact of pulse pressure on clinical outcome in extracorporeal cardiopulmonary resuscitation (eCPR) patients
Authors: Rilinger J , Riefler A M , Bemtgen X , Jaeckel M , Zotzmann V , Biever P M , Duerschmied D , Benk C , Trummer G , Kaier K , Bode C , Staudacher D L , Wengenmayer T
Published: October 2021

Background

Hemodynamic response after successful extracorporeal cardiopulmonary resuscitation (eCPR) is very heterogeneous. Pulse pressure (PP) as an easy to access surrogate parameter and correlate for myocardial damage or recovery from it, might be a valuable tool to estimate the outcome of these patients.

Purpose

To investigate the predictive value of the surrogate parameter PP in eCPR patients.

Methods

We report retrospective data of a single-centre registry of eCPR patients, treated at our Interdisciplinary Medical Intensive Care Unit between 01/2017 and 01/2020. The association between PP of the first 10 days after eCPR and hospital survival was investigated. Moreover, patients were divided into three groups according to their PP (low (0–9 mmHg), mid (10–29 mmHg) and high (≥30 mmHg)) at each time point.

Results

143 patients (age 63 years, 74.1% male, 40% OHCA, average low flow time 49 min) were analysed. Overall hospital survival rate was 28%. A low PP both early after eCPR (after 1, 3, 6 and 12 hours) and in the further course after day 1 to day 8 was associated with reduced hospital survival. At each time point (1 hour to day 5) the classification of patients into a low, mid and high PP group was able to categorize the patients for a low (5–20%), moderate (20–40%) and high (50–70%) survival rate. A multivariable analysis showed that the mean PP of the first 24 hours was an independent predictor for survival (p=0.008, figure 1).

Conclusion

In this analysis, PP occurred to be a valuable parameter to estimate survival and maybe support clinical decision making in the further course of patients after eCPR.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Survival of eCPR patients by mean 24hPP
Coronary microvascular function in patients with angina with no obstructive coronary artery disease-What factors affect it clinically or angiographically?
Authors: Teragawa H , Akazawa R , Oshita C , Uchimura Y , Orita Y
Published: October 2021

Background

In the clinical setting, we have often experienced patients with angina with no obstructive coronary artery disease (ANOCA), and it has been proposed that the presence of coronary microvascular dysfunction (CMD) play a pivotal role in the pathogenesis of ANOCA. Thus, it is important to assess coronary microvascular function (CMF). However, it has not been clarified what clinical factors or lesion characteristics on coronary angiography (CAG) affect CMF. Thus, we investigated the relationship between CMF and clinical factors or lesion characteristics on CAG in patients with ANOCA.

Methods

Thirty-four patients with chest pain, who underwent CAG, spasm provocation test (SPT) and CMF test, were enrolled. We excluded patients who had moderate coronary stenosis (% stenosis >30%). In the SPT with acetylcholine for left coronary artery and right coronary artery (RCA), the coronary spasm was defined as >90% narrowing of coronary artery on CAG accompanied with chest symptoms and/or ST-T changes on ECG during SPT, and coronary microvascular spasm (MVS) was defined as ≤90% narrowing of coronary artery on CAG with accompanied with chest pain and ST-T changes during SPT. In each coronary artery, the presences of atherosclerosis (20%≤%stenosis≤30%), focal spasm (spasm occurred within one segment of AHA classification), diffuse spasm (spasm occurred over two segments of AHA classification) and MVS, were checked. In the CMF test with a pressure-wire during adenosine triphosphate infusion, the index of microvascular resistance (IMR) was measured. IMR values were obtained in 34 of the left anterior descending coronary artery (LAD) and 12 in RCA. In each patient, conventional coronary risk factors, blood chemical parameters, peripheral endothelial function such as flow-mediated dilation (FMD) of brachial artery and left ventricular mass index (LVMI) were checked.

Results

In 34 patients, clinical factors including blood chemical parameters, FMD and LVMI, except for smoking status did not affect IMR values on LAD. Only the smoking status was associated with IMR values as follows: median IMR values were 44, 22 and 25 in current smokers (n=5), past smokers (n=8) and never smokers (n=21, p=0.03), respectively. In 46 coronary arteries, the presence of atherosclerosis, the type of the coronary spasm, such as focal and diffuse spasm and MVS, did not affect the IMR values, however, it was significantly higher in the RCA (median 38) than that in the LAD (median 26, p=0.02).

Conclusion

These results suggest that smoking status affected CMF in patients with ANOCA, suggesting the possibility of improvement of CMF by stop smoking in such patients. In addition, in the assessment of CMF, it may be important to take into account which coronary artery being evaluated.

Funding Acknowledgement

Type of funding sources: None.
Myocardial ischaemia of non-obstructive origin as a cause of new onset anginal chest pain in the long COVID syndrome
Authors: Espejo C , Mejia-Renteria H , Travieso A , Gonzalo N , Fernandez S , Capote M L , Vedia O , Wang L , Nunez-Gil I , Grande Ingelmo J M , Fernandez Rozas I , Olmos C , Vivas D , Escaned J
Published: October 2021

Background

New-onset chest pain occurs in around 20% of patients with long COVID syndrome (LCS). Being the vascular endothelium one of the targets of the SARS-CoV-2 virus, we hypothesized that new onset anginal symptoms in LCS could be due to endothelium dysfunction and other non-obstructive causes of myocardial ischaemia.

Methods

We investigated 11 consecutive patients who developed new onset anginal chest pain, suggestive of myocardial ischaemia, after documented SARS-CoV-2 infection. Intracoronary assessment included endothelium-dependent evaluation with acetylcholine testing (Ach), and endothelium-independent assessment with coronary flow reserve (CFR) and microcirculatory resistance (MR). Criteria for positiveness of these tests and medical treatment recommendation were obtained from 2019 ESC guidelines and 2020 EAPCI consensus document on ischaemia with non-obstructive coronary arteries (INOCA).

Results

Mean patient age was 56 years (SD ± 15); 10 (91%) were female. In the acute COVID-19 phase, 4 patients (36%) had had pulmonary infiltrates and 2 (18%) required hospitalization. Conclusive non-invasive tests were obtained in 7 (64%), showing exercise-related myocardial ischaemia in 6 (86%). Coronary angiography ruled out obstructive epicardial stenoses in all the patients. Ach testing revealed abnormal endothelium-dependent responses in 9 (82%) patients: 5 (56%) had epicardial vessel and 4 (44%) microvascular spasm. Endothelium-independent assessment was abnormal in 6 (54%) cases, with abnormal CFR in 2 (33%), abnormal MR in 2 (33) and both abnormal CFR and MR in 2 (33%) patients. The most frequent endotype was combined endothelium dependent- and independent abnormalities (6/9, 67%). Stratified medical treatment according to endotype led to significant improvement in Seattle Angina Scores for angina frequency (+22 points, p=0.013) and a notable trend towards angina stability (+25 points, p=0.093) at a mean follow-up time of 222 days.

Conclusions

Myocardial ischaemia of non-obstructive origin is common in patients with chest pain and LCS. Vasomotor abnormalities related to endothelial dysfunction occurred in 82% of patients, frequently associated to impaired microvascular vasodilation or high microvascular resistance. Stratified medical treatment led to significant improvement in angina stability and frequency.

Funding Acknowledgement

Type of funding sources: None.
Transmyocardial extraction of endothelin-1 correlates with increased microvascular resistance following percutaneous coronary intervention
Authors: Abraham G R , Nyimanu D , Kuc R , Maguire J , Davenport A P , Hoole S P
Published: October 2021

Introduction

Coronary microvascular dysfunction (CMD) can persist following successful percutaneous coronary intervention (PCI). Endothelin-1 (ET-1) is a potent vasoconstrictor and may be an important mediator of CMD. We sought to assess the trans-myocardial gradient (TMG – coronary sinus minus coronary root levels) of ET-1 and its precursor - Big ET-1 and assess the correlation with pressure-wire indices of CMD: coronary flow reserve (CFR) and index of microvascular resistance (IMR).

Methods

Paired blood samples from the aortic root and coronary sinus were collected before and after pressure wire guided PCI from patients with stable angina. Plasma was then analysed using specific enzyme linked immunosorbent assay (ELISA) for quantification of ET-1 and Big ET-1 and correlated with pressure-wire data.

Results

Samples were analysed from 66 patients. Both mean ET-1 and Big ET-1 concentrations increased post-PCI in both the aorta (ET-1: 1.0±0.4 pg/ml to 1.4±0.4 pg/ml, p<0.0001 and Big ET-1: 2.8±1.3 pg/ml to 3.4±1.6 pg/ml, p<0.0001) and coronary sinus (ET-1: 1.0±0.3 pg/ml to 1.2±0.3 pg/ml, p=0.03 and Big ET-1: 3.2±1.7 pg/ml to 3.8±1.5 pg/ml, p=0.01). TMG extraction of ET-1 increased following PCI: 0.05±0.25 pg/ml vs.-0.20±0.41 pg/ml, p=0.01. In contrast, there was TMG release of Big ET-1 before and after PCI: 0.46±1.26 pg/ml vs. 0.38±1.03 pg/ml, p=0.52. ET-1 extraction correlated with IMR post-PCI (Pearson's r=0.293, p=0.02). Patients with CFR<2 post-PCI demonstrated a numerical trend towards higher mean ET-1 extraction than those with preserved CFR post-PCI (0.30±0.51 pg/ml vs. 0.16±0.42 pg/ml, p=0.31) as did those with criteria for Type 4a Myocardial Infarction compared with those without (0.39±0.57 vs. 0.15±0.41, p=0.11).

Conclusions

ET-1 and Big ET-1 significantly increase post-PCI. Trans-myocardial extraction of ET-1 increases post-PCI and correlates with post-PCI CMD.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Jon Moulton Charity Trust.NIHR Cambridge Biomedical Research Centre Biomedical Resources Grant. TMG of ET-1 and Big ET-1ET-1 extraction and post-PCI IMR
Type 2 diabetes, chronic kidney disease and major cardiovascular events in patients with established coronary artery disease
Authors: Sprenger L , Vonbank A , Larcher B , Mader A , Maechler M , Mutschlechner B , Benda M , Leiherer A , Muendlein A , Drexel H , Saely C H
Published: October 2021

Both type 2 diabetes (T2DM) and chronic kidney disease (CKD) confer a high risk of cardiovascular disease (CVD), and these conditions frequently coincide.

The purpose of this study was to investigate the single and joint effects of T2DM and CKD on major cardiovascular events (MACE) in a high-risk population of patients with established coronary artery disease (CAD).

We prospectively investigated 1460 patients with angiographically proven CAD over 10.4±4.8 years, of whom 454 (30.8%) had T2DM and 251 (17.1%) had CKD.

MACE occurred more frequently in T2DM patients than in non-diabetic subjects (40.4% vs 28.7%, p<0.001) and in patients with CKD (eGFR <60ml/min/1.73m2) than in those with an eGRF ≥60ml/min/1.73m2 (51.6% vs 28.3%, p<0.001). When both, T2DM and CKD were considered, 863 subjects had neither T2DM nor CKD, 346 had T2DM but not CKD, 148 did not have diabetes but had CKD, and 103 had both T2DM and CKD. When compared with the incidence of MACE among patients with neither T2DM nor CKD (25.3%), MACE occurred more frequently in patients with T2DM who did not have CKD (35.8%; p<0.001) as well as in non-diabetic patients with CKD (47.6%; p<0.001) and occurred most freuently in patients with both, T2DM and CKD (57.4%; p<0.001), in whom the incidence of MACE was higher than in those with T2DM but not CKD (p<0.001) or those without T2DM but with CKD (p=0.025); the incidence of MACE was higher in non-diabetic CKD patients than in T2DM patients who did not have CKD (p=0.041). In Cox regression analysis, T2DM (HR=1.46 [1.20–1.78]; p<0.001) and CKD (HR=1.81 [1.45–2.27]; p<0.001) were mutually independent predictors of MACE after multivariate adjustment.

We conclude that T2DM and CKD are mutually independent risk factors for MACE in patients with established CAD. CAD patients with both CKD and T2DM are an extremely high risk for MACE.

Funding Acknowledgement

Type of funding sources: None.
Acute kidney injury definition following PCI and cardiovascular outcomes
Authors: Skalsky K , Levi A , Bental T , Vaknin-Assa H , Assali A , Steinmetz T , Kornowski R , Perl L
Published: October 2021

Background

Acute kidney injury (AKI) is a complication of percutaneous coronary intervention (PCI), known to increase rates of adverse medical events. We aimed to identify the optimal definition of AKI in predicting of adverse cardiovascular outcomes and mortality post PCI.

Methods

From a large registry of patients undergoing PCI between 2006–2018 (n=25,690) at two hospitals, consecutive patients were assessed for the presence of AKI according to four different definitions: a relative elevation of ≥25% or ≥50%; or an absolute elevation of ≥0.3 mg/dL or ≥0.5 mg/dL in serum creatinine at 48 hours post PCI. We assessed the calculated rates of AKI according to the different definitions. The discriminant capacity for 30-day and 1-year mortality and MACE (MACE: all-cause death, myocardial infarction, target-vessel revascularization and coronary artery bypass graft surgery) of each definition was calculated using ROC curves and AUCs.

Results

Data of 15,153 patients was available for final analysis. Rates of AKI were 12.1%, 3.2%, 8.1% and 3.9% according to the four definitions, respectively. The discriminant capacity of adverse outcomes was highest among those defined as AKI according to the third definition - an absolute elevation of ≥0.3 mg/dL in serum creatinine with an AUC of 0.82 (95% CI 0.80–0.84) for 30-day mortality (P value = 0.036) and an AUC of 0.78 (CI 0.76–0.79) for 30 days MACE.

Conclusions

An absolute elevation of ≥0.3 mg/dL in serum creatinine 48 hours post PCI predicts overall mortality and MACE most accurately.

Funding Acknowledgement

Type of funding sources: None.