bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of sodium-glucose co-transporter 2 inhibitors on left ventricular mass and left atrial volume indices assessed either by cardiovascular magnetic resonance or transthoracic echocardiography
Authors: Patoulias D , Boulmpou A , Tranidou A , Doumas M , Vassilikos V , Papadopoulos C.E
Published: October 2021

Background

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel class of antidiabetic regimens linked with a significant reduction in the risk for surrogate cardiovascular and renal outcomes. Specific patient populations, for example subjects with heart failure with reduced ejection fraction (HFrEF), also benefit from this drug class, regardless the presence of T2DM. Left ventricular (LV) hypertrophy is a strong, independent predictor of cardiovascular morbidity and mortality; left atrial volume index (LAVI), an indicator of severity of LV diastolic dysfunction and filling properties, has been shown to predict “hard” cardiovascular outcomes among patients with T2DM, while it might predict the recovery of left ventricular ejection fraction in patients with HFrEF.

Purpose

We sought to determine the effect of SGLT-2 inhibitors on the above indices, in order to evaluate additional cardioprotective mechanisms of this drug class.

Methods

We searched 2 major electronic databases (PubMed and Cochrane/CENTRAL) along with grey literature sources for parallel-group RCTs investigating the effect of SGLT-2 inhibitors compared to placebo or active control on LV mass, LV mass index (LVMI) and LAVI, evaluated either by TTE or CMR, on adult patients regardless the presence of T2DM or HF.

Results

After screening the potentially eligible records, 9 studies were included in our analysis with a total of 843 patients. Treatment with SGLT-2 inhibitors compared to placebo or active control leads to a statistically significant decrease in LV mass by 6.01 g (95% CI −11.33 to −0.69, I2=76%) (Figure 1a). A significant decrease in LVMI by 2.61 g/m2 was observed (MD=−2.61, 95% CI −4.94 to −0.29, I2=65%) (Figure 1b). Of note, the effect on LAVI was marginally non-significant (MD=−1.51 ml/m2, 95% CI −3.05 to 0.03, I2=0%) (Figure 1c). Subgroup analysis for patients with HFrEF demonstrated a non-significant reduction in LV mass (MD=−11.72 g, 95% CI −30.61 to 7.16, I2=90%) and in LVMI (MD=−6.28 g/m2, 95% CI −30.61 to 0.25, I2=80%) (Figure 2a and 2b).

Conclusions

SGLT-2 inhibitors demonstrate a clear benefit on LV mass and LVMI, regardless of diabetes status, while a marginally non-significant effect is observed on LAVI. These results provide further insights into the cardioprotective mechanisms mediated by this drug class, besides those already established.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Door-to-Furosemide time effects on in-hospital mortality and length of stay in acute heart failure patients
Authors: Viriyanukulvong K.V , Han-Gla A.H , Phannajit J.P , Ariyachaipanich A.A
Published: October 2021

Background

Acute heart failure (AHF) is a common cause of hospitalization and mortality. Time-to-therapy concept may help improve in-hospital outcomes.

Objective

To evaluate In-hospital outcomes after receiving early versus delayed furosemide injection among AHF patients.

Method

Retrospective single-center cohort study included patients who were admitted with AHF through ED during 1 July 2017 to 31 Dec 2019. Door-to-furosemide (D2F) time was defined as the time from patient arrival at the ED to the first intravenous furosemide injection within 24 hours. Patients with a D2F time ≤60 min were classified as the early treatment group. Primary outcome was in-hospital mortality and secondary outcomes were in-hospital morbidities. Adjusted odd ratio and the 95% confidence interval (CI) were represented using multiple logistic regression adjusted for age, sex, weight, furosemide dose, and baseline serum creatinine.

Results

Among 820 enrolled AHF patients, the median D2F time was 80.5 min (interquartile range: 42 to 187 min). of those 324 (39%) patients were categorized into early D2F time group. The rate of total in-hospital death was 4.9% and did not differ between groups (3.1% vs. 6%, early vs delayed D2F group; p=0.067). In multivariate analysis, early treatment is not significantly associated with lower in-hospital mortality (odd ratio: 0.57; 95% CI: 0.27–1.23; p=0.152) as well as secondary endpoints.

Conclusions

In this small single-center study, early treatment with furosemide was uncommon. Less than half of admitted patients were received furosemide within 1 hour. In-hospital mortality was double in delayed group but was not statistically significant.

Funding Acknowledgement

Type of funding sources: None.
Validation of a novel framework defining the acceptable standard of care for heart failure with reduced ejection fraction
Authors: Lopes P , Albuquerque F , Freitas P , Presume J , Rocha B , Cunha G , Strong C , Tralhao A , Trabulo M , Ferreira J , Ventosa A , Aguiar C , Mendes M , Ferreira A
Published: October 2021

Background

In heart failure with reduced ejection fraction (HFrEF), uptitration of neurohormonal antagonists to trial-proven doses shown to reduce mortality is challenging and seldomly achieved in clinical practice. A major reason for underdosing of these agents is the lack of a clear description of what constitutes an acceptable standard of care in HFrEF. To address this limitation, a novel framework for describing the physician adherence to evidence-based treatment was recently proposed. The aim of our study was to evaluate and validate the proposed framework in a real-world population of patients with HFrEF.

Methods

A cohort of patients with HFrEF, defined as left ventricular ejection fraction (LVEF) <40%, under treatment with neurohormonal antagonists for at least 3 months were retrospectively identified at a tertiary hospital's Heart Failure Clinic. Demographic, clinical, echocardiographic and treatment data were assessed. Patients were divided in three strata for each neurohormonal antagonist, according to the proposed framework: Status I – patients receiving target doses or the highest tolerated dose; Status II – use of subtarget doses for reasons unrelated to clinically important intolerance; and Status III – not receiving the drug at any dose. The prognostic value of each strata was assessed for all-cause mortality.

Results

A total of 408 patients (mean age 68±12 years, 78% male, 63% ischemic etiology) were included. The median LVEF was 31% (IQR 25–36) and most patients were in NYHA class II or III [210 (51.5%) and 163 (40%), respectively]. Medical therapy is described in Table 1. During a median follow-up of 3.3 years (IQR 1.4–5.6), 210 patients died. On univariable analysis, achieving Status I of beta-blocker (BB) therapy (HR: 0.50; 95% CI: 0.32–0.81; P=0.004) or ACEi/ARB (HR: 0.56; 95% CI: 0.36–0.86; P=0.012) was associated with reduced all-cause mortality. The mortality of patients in Status II of BB or ACEi/ARB was similar to the mortality of those not receiving the drug (HR for BB: 0.90; 95% CI: 0.53–1.52; P=0.69 and HR for ACEi/ARB: 0.71; 95% CI: 0.42–1.18; P=0.182) – figure 1. Achieving Status I of BB remained independently associated with reduced mortality after adjustment for several clinical and echocardiographic confounders (n=13) (adjusted HR: 0.59; 95% CI: 0.35–0.98; P=0.041).

Conclusions

In this real-world population of patients with HFrEF, the vast majority of patients were in Status I of BB and ACEi/ARB therapy. Achieving Status I of BB therapy seems to be associated with reduced mortality, even after adjustment for several markers of disease severity, highlighting the need for uptitration of medical therapy to maximal tolerated doses according to trial-proven regimens.

Funding Acknowledgement

Type of funding sources: None.
Impact of phosphodiesterase-5 inhibitors on right ventricular function and exercise capacity after left ventricular assist-device implantation: the PIVAD study
Authors: Jakstaite A , Papathanasiou M , Tonscheidt W , Mincu R , Wernhart S , Pizanis N , Schmack B , Kamler M , Weymann A , Ruhparwar A , Rassaf T , Luedike P
Published: October 2021

Background

Long-term therapy with oral phosphodiesterase-5 inhibitors (PDE5I) is frequently implemented after left ventricular assist-device (LVAD) implantation to improve hemodynamics and prevent late-onset right ventricular (RV) failure or to facilitate listing for heart transplantation in individuals with persistent pulmonary hypertension. The safety and efficacy of this appoach has not been prospectively studied. Recent analyses of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) demonstrated improved survival for patients under long-term PDE5I after 48 months but higher incidence of early postoperative RV failure as well as a higher risk for gastrointestinal bleeding.

Purpose

To evaluate the impact of discontinuation of PDE5I in patients on LVAD support.

Methods

In this prospective, single-arm, interventional study we enrolled LVAD recipients on oral PDE5I (sildenafil or tadalafil) after at least 1 month post-implant who were clinically stable on optimal medical therapy. The patients underwent physical examination, ECG, 6-minute walking test, cardiopulmonary exercise testing, transthoracic echocardiography, LVAD interrogation, questionnaire based evaluation of quality of life and testing of serum biomarkers at baseline and 4 weeks after discontinuation of oral PDE5I therapy.

Results

From 10/2019 to 02/2021 thirty patiens were included in the study and completed the follow-up. Mean age was 54 years, 90% were male. Destination therapy was the primary treatment goal in 13% of this cohort while 87% received LVAD as a bridge to transplant. Mean dosis of tadalafil was 24.6 mg, of sildenafil 42.5 mg. At follow-up no significant changes were elicited in echocardiographic markers of RV function, peak oxygen consumption, VE/VCO2 slope, eGFR, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration, quality of life and average flow and power readings of the device but mild increase in walking distance (Table 1). Two patients were hospitalized for non-cardiac reasons (subtherapeutic INR, driveline infection). No patient was hospitalized for cardiac decompensation.

Conclusion

Discontinuation of PDE5I was not associated with deterioration of RV function, exercise capacity and quality of life after 4 weeks. The risk/benefit profile of PDE5I in LVAD patients needs to be further investigated in context of randomized controlled trials.

Funding Acknowledgement

Type of funding sources: None. Table 1
The impact of psychiatric diagnoses on two-year outcomes in patients with ventricular assist devices
Authors: Tolia S , Ahmed S , Adams J , Morreale C , Paliga R , Aicher T , Coyle L , Narang N , Pillarella J , Joshi A , Sciamanna C , Tatooles A , Pappas P , Cotts W , Andrade A
Published: October 2021

Background

A multi-specialty approach is required during patient selection for left ventricular assist device (LVAD) implantation. In addition to a comprehensive medical evaluation, patients undergo an extensive psychiatric work up to ensure their candidacy when pursuing durable support devices. We aim to analyze the impact of psychiatric illnesses on 2-year outcomes after VAD implantation.

Methods

This study was a single center, retrospective analysis of 263 patients who underwent durable LVAD implantation between 2015 and 2017. All patients were evaluated by a single specialist during their work up for LVAD implantation. Patients who had a pre-existing diagnosis defined by criteria outlined in Diagnostic and Statistical Manual of Mental Disorders (DSM-5) were assigned to the History of Psychiatric Diagnosis group. Statistical analysis was performed using Chi-Square and Student's t-tests, wherein p<0.05 was considered statistically significant.

Results

Of the 263 patients, 68 patients were found to have a history of psychiatric illness compared to 195 who had no previous diagnosis. Of those with a psychiatric history, 30.8% had Depression, 1.5% had Bipolar disorder, 22.1% had Anxiety, 1.5% had PTSD, and 16.2% had more than one diagnosis. 19.5% of patients with no history went on to be transplanted compared to 22.1% of patients with a psychiatric history (p=0.65). No significant difference was found between length of stay, days to readmission, 30-day survival, and 2-year survival. Patients without a psychiatric history were found to have fewer number of readmissions over 2 years (p<0.01) (See Table). No significant difference was seen in complications including driveline infections, bacteremia, cerebrovascular accidents, pump thromboses, pump hemolysis, or major bleeding events (See Table).

Conclusion

Psychosocial characteristics play a significant role in determining a patient's candidacy for LVAD implantation. Although patients with a history of psychiatric illness were found to have a greater number of readmissions, this did not correlate to poorer outcomes or increased morbidity and mortality over 2 years. This study highlights the importance of taking a multi-faceted approach when determining patient eligibility for mechanical support devices. Future studies with larger population models should be conducted.

Funding Acknowledgement

Type of funding sources: None.
Echo-guided LVAD speed optimization for exercise maximization
Authors: Stapor M , Pilat A , Gackowski A , Gorkiewicz-Kot I , Kleczynski P , Zmudka K , Legutko J , Kapelak B , Wierzbicki K
Published: October 2021

Background

Continuous-flow left ventricular assist devices (LVAD) are becoming a destination therapy in patients with end-stage left ventricular dysfunction and a competitive method for heart transplantation. Current generation pumps operate with a fixed rotation speed and do not have the automatic speed adjustment capability. However, it was shown that acceleration of the pump speed during stress test increases the maximum exercise tolerance.

Purpose

The study aimed to evaluate the concept of dynamic pump speed optimization based on the echocardiographic assessment of aortic valve opening (AVO) during the cardiopulmonary exercise test (CPET).

Methods

Patients with implanted third-generation centrifugal continuous-flow LVAD's with hydrodynamic bearing were prospectively included. Two CPET's were performed after resting speed optimization. The first one with maintained baseline pump speed settings, and the second one with gradually increased speed depending on live echocardiographic imaging. The sequence of tests was random.

Results

Exercise AVO was apparent in all 22 included patients. The resting pump speed was 2691 RPM and incremented on average by 566 RPM (20%). Pump power and flow raised from 5.6 to 9.8 Watts (p<0.0001) and from 5.8 to 7.3 l/min (p<0.0001), respectively. Peak VO2 increased from 11.1 to 12.8 ml/kg/min (p=0.0003) and maximum workload from 1.1 to 1.2 W/kg (p=0.03). The Borg scale exertion level decreased from 15.2 to 13.5 (p=0.0049). There was a visible trend towards longer exercise time (36s) but no statistical significance was achieved (p=0.1).

Conclusion

Ultrasonographic AVO analysis is possible during CPET's in patients supported with LVAD. Dynamic echo-guided pump speed adjustment based on the AVO improves exercise tolerance, augments peak VO2 consumption and maximal workload. An automatic speed adjustment in the next generations of LVAD controllers might improve functional capacity and requires further basic, technological and clinical research.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): 1. Cor Aegrum Foundation of Cardiac Surgery Development in Cracow2. Medtronic Poland Sp. z o.o.
Left ventricular longitudinal shortening at cardiac base as a determinant of left atrial reservoir function in cardiac amyloidosis
Authors: Inoue K , Nakao Y , Saito M , Kinoshita M , Higaki R , Higashi H , Ikeda S , Yamagushi O
Published: October 2021

Objective

To investigate a mechanistic determinant of left atrial (LA) reservoir function in patients presenting left ventricular (LV) hypertrophy, and clarify diagnostic and prognostic values of LA reservoir strain in patients with cardiac amyloidosis (CA).

Methods

Three-hundred sixty patients (median age: 68 years, male gender: 65%) with left ventricular hypertrophy (LVH) assessed by echocardiography were retrospectively included. The LVH etiologies were diagnosed by any of biopsy, cardiac magnetic resonance imaging or 99mTc-PYP scintigraphy. LV segmental longitudinal strain was estimated from apical three views, and LA reservoir strain was measured from an apical 4-chamber view.

Results

The LVH etiologies were confirmed with CA in 81 patients, hypertensive heart disease in 87 patients, hypertrophic cardiomyopathy in 143 patients, and miscellaneous disorders in 49 patients. The median (25th, 75th percentile) value of LV ejection fraction was 59% (48–67). LV basal longitudinal strain and LA reservoir strain were significantly reduced in patients with CA compared with those with other etiologies; LV basal strain: 5.4% (3.9–8.7) vs. 11.9% (9.3–14.6), LA reservoir strain: 9.2% (6.3–12.3) vs. 17.5% (11.3–24.1), p<0.01 respectively. LV basal strain was significantly correlated with LA reservoir strain in patients with CA (r=0.57, p<0.01) and in those with other etiologies (r=0.45, p<0.01). The area under the receiver-operating characteristic curves of LA reservoir strain and E/e' (0.78 and 0.74) to identify CA etiology were significantly larger than that of LA volume index (0.62) (p<0.01). During the follow-up period (median 2.9 years), 53 patients experienced heart failure hospitalization. The Cox regression model including age, gender, LV ejection fraction, E/e' and LA reservoir strain showed that male gender (hazard ratio: 0.46, p=0.03), E/e' (hazard ratio: 1.04, p<0.01) and LA reservoir strain (hazard ratio: 0.94, p<0.01) independently predicted heart failure hospitalization.

Conclusions

The decrease of LV longitudinal shortening at cardiac base could worsen LA reservoir function especially in patients with CA. LA reservoir strain might be an alternative measure to identify CA etiology and have a predictive value of heart failure hospitalization in patients with LV hypertrophy.

Funding Acknowledgement

Type of funding sources: None.
Immunological monitoring in cardiac allograft vasculopathy
Authors: Alyaydin E , Welp H , Pistulli R , Dell Aquila A , Sindermann J , Tuleta I , Reinecke H , Pogoda C.A
Published: October 2021

Background

The interaction of immunological determinants and classic cardiovascular risk factors can accelerate the development of cardiac allograft vasculopathy (CAV) with deleterious consequences for the graft function in heart transplantation (HTx). When it comes to immunological risk assessment, inverse CD4/CD8 ratio can be a poor prognostic marker in coronary artery disease, but its influence is unclear in CAV.

Aim

To evaluate the role of the T-lymphocyte count in peripheral blood as well as CD4/CD8 ratio as a predictive marker for CAV severity in a very long-term follow-up after HTx.

Methods

We performed a retrospective analysis of patient data collected during routine clinical follow-up visits. These data included innate and adaptive immune cell count in peripheral blood (lymphocyte count, CD3+, CD4+, CD8+ and CD19+ T cells and NK cells).

Results

The study population consisted of 174 patients with a mean follow-up of 13.1±6.5 years and a mean age at the time of HTx of 45.2±15.0 years. CAV was diagnosed in 71 patients (40.8%), more than half of which underwent interventional procedure or surgical therapy (n=40, 56.3%). A comparison of the cytoimmunological profile of patients with no CAV or mild disease (group 1, n=134) vs. with CAV requiring treatment (group 2, n=40), revealed significantly reduced percentage of CD4+ T cells (46.4±11.4% vs. 41.2±9.6%, p=0.01) and elevated percentage of CD8+ T lymphocytes in group 2 (28.3±14.1% vs. 35.8±13.7%, p=0.003). Thus, the CD4/CD8 ratio was altered in therapy requiring CAV (2.3±2.0 vs. 1.5±1.0, respectively, p<0.001). However, we observed no differences in the absolute count of T-helper cells (CD4+ T cells: 692.2±329.2 vs. 653.8±390.5 cells/μL, p=0.54) and cytotoxic T lymphocytes (CD8+ T cells: 474.7±450.2 vs. 600.0±469.0 cells/μL, p=0.13). Further analysis showed no differences regarding lymphocyte count and absolute count or percentage of CD3+ and CD19+ T cells as well as NK cells. Inverse CD4/CD8 ratio (<1) was associated with greater risk for therapy requiring CAV (OR 2.8, 95% CI 1.3 – 5.9, p=0.009) in a univariate logistic regression analysis.

Conclusions

Decreased CD4+ T cell count along with increased cytotoxic T lymphocyte count resulting in inverse CD4/CD8 ratio is associated with increased CAV severity in HTx. Given the possible interactions with the immunosuppressive agents and prednisolone, monitoring of the cytomimmunological profile can help identify patients at risk and be useful in establishing therapeutic strategies.

Funding Acknowledgement

Type of funding sources: None.
Non-sustained ventricular tachycardia on remote patient monitoring in heart failure patients
Authors: Barradas Da Silva M , Duarte F , Oliveira L , Serena C , Fontes A , Monteiro A , Machado C , Dourado R , Santos E , Pelicano N , Pacheco M , Tavares A , Martins D
Published: October 2021

Background

Non-sustained ventricular tachycardia (NSVT) is commonly found in patients with structural heart disease and was historically obtained from registers of external ambulatory monitoring. The advent of remote patient monitoring (RPM) in Cardiac implantable electronic devices (CIEDs) has made it possible to detect asymptomatic NSVT in Heart Failure (HF) patients more frequently, but its impact in real world is uncertain.

Purpose

To determine the clinical impact of NSVT detection in RPM in ischemic and non-ischemic chronic heart failure patients with reduced ejection fraction (HFrEF) and CIEDs.

Methods

We retrospectively enrolled 121 consecutive patients with HFrEF, CIEDs and RPM. Patients were evaluated through routine episodic CIEDs interrogation, routine clinical evaluations and continuous monitoring data obtained from CIEDs and transmitted remotely to the care team and divided into NSVT positive (Group 1) and negative groups (Group 2). Primary endpoint was admissions to the emergency department by HF decompensation and secondary endpoint was the occurrence of arrhythmic events. A sub-analysis of non-ischemic HF was also performed.

Results

NSVT was detected in 78 (72,2%) patients. The mean number of episodes of NSVT was 611,68±3271,25 during the follow-up period or 2,445±16,688 in 24 hours. Mean age was 62,40±13,218 years, 71,9% were males and mean follow-up period was 56,30±39,37 months. Fifty-eight patients (47,9%) had transvenous implantable cardioverter defibrillator (ICD), 48 (39,7%) implantable cardiac resynchronization therapy (CRT) defibrillator (CRT-D), 14 (11,6%) subcutaneous ICD (S-ICD) and 1 (0,8%) CRT pacemaker (CRT-P). Medium left ventricular ejection fraction (LVEF) was 34,70±12,53%, 25 (23,14%) were in NYHA III-IV and 46 (39,0%) were ischemic (29 (37,7%) in Group 1 and 11 (37,9%) in Group 2). NSVT was associated with the occurrence of sustained ventricular tachycardia (VT) (1,88±0,186episodes of VT in group 1 and 0,03±0,186 in group 2, p=0,012), ventricular fibrillation (VF) (1,44±5,325 episodes of VT in group 1 and 0,03±0,186 in group 2, p=0,011) and admissions to the emergency department by HF decompensation at 5 years (r=0,310, p=0,011). A sub-analysis in non-ischemic HF patients also showed correlation between NSVT and VT (r=0,602, p<0,05) and admissions to the emergency department by HF decompensation at 5 years (r=0,382, p=0,014).

Conclusions

On remote patient monitoring with CIEDs, NSVT in HF patients was associated with arrhythmic events and may serve as a predictor for HF decompensations.

Funding Acknowledgement

Type of funding sources: None.
Cardiac function in fetal and infants born to mothers with gestational diabetes
Authors: Iwashima S , Yamamoto Y , Takahashi K
Published: October 2021

Background

The intraventricular pressure differences (IVPD) IVPD using color M-mode is a specific marker in infants of mothers with gestational diabetes mellitus (GDM). (Circulation R 2019, 378–388).

Purpose

This study investigated the myocardial performance of fetuses in mothers with GDM under the new GDM definition.

Method

The study population comprised of 27 mothers with GDM and the fetus. Women with GDM were defined as those with a glucose metabolism abnormality that existed before or began during the current pregnancy and was diagnosed using OGTTs. The 5 mothers with type 1 or type 2 DM were receiving insulin before their pregnancy. Fetal echo measurements were performed about median gestational age 35 weeks. The primary outcomes were comparisons of the fetal myocardial performance of GDM with insulin administration and without administration using echocardiography with IVPD, and IVPG. The secondary outcome has investigated the relationships between echocardiography parameters, IVPD, and IVPG, and maternal factors. For all statistical analyses, P<0.05 was considered significant.

Result

In the insulin group was higher RV output (Fig. 2A). Maternal max HbA1c was observed to have a positive correlation with fetal RV output, significantly (Fig. 2B). Maternal max fasting blood glucose was observed to have a negative correlation with the Total, Basal and Mid to apical IVPD, significantly, respectively. Serial change of LV Total IVPD from fetal to after birth shown in Slide. In both groups, LV Total IVPD was increasing from fetal and after birth significantly.

Conclusion

The mechanism associated with the favorable systolic and diastolic performances in IGDMs is suggested to involve metabolic adaptations in the heart. In diabetic mice, these adaptations seem to prevent the heart from failing during conditions of pressure overload, suggesting a restoration of the balance between glucose and fatty acid utilization is beneficial for cardiac function. In fetal LV and RV-IVPD might be interacted the mother's blood sugar control. These indexes can predict the sensitive fetal and infant's cardiac dysfunction for GDM.

Funding Acknowledgement

Type of funding sources: None.
Relation of left atrial function with exercise capacity and muscle endurance in patients with heart failure
Authors: Bekfani T , Ijuin S.H , Hamadanchi A , Bekhite M , Nisser J , Derlien S , Westphal J , Bogoviku J , Morris D.A , Fudim M , Braun-Dullaeus R.C , Moebius-Winkler S , Schulze P.C
Published: October 2021

Aims

Left atrial strain (LAS) and skeletal muscle endurance demonstrate a linear relationship to peak VO2. Less is known about the relationship between central (cardiac) and peripheral (muscle endurance) limitations of exercise capacity in patients with heart failure (HF). We investigated this relationship using novel cardiac markers such as LAS and left atrial ejection fraction (LAEF).

Methods

We analysed echocardiographic measurements, cardiopulmonary exercise testing, and isokinetic muscle function in 55 subjects with HF and controls (17 heart failure with preserved ejection fraction -HFpEF, 18 heart failure with reduced ejection fraction-HFrEF and 20 healthy controls).

Results

Patients with reduced LAEF showed reduced peak VO2: 14.3±3.5 vs. 18.5±3.5 ml/min/kg, p=0.003 and reduced muscle endurance (RME): 64.3±23.9 vs. 88.5±32.3 Nm/kg, p=0.028. Patients with reduced LAS showed similar results. Neither left ventricular global longitudinal strain (LVGLS) nor left atrial volume index (LAVI) were associated with RME. The area under the curve of LAS and LAEF in patients with HF in association with RME were (0.76 vs. 0.80) with 95% confidence interval (CI) (0.59–0.96, p=0.012 vs. 0.63–0.98, p=0.006, respectively). Peak torque of the left leg was associated with E/LAS (E: early diastolic) in patients with HFpEF (r=−0.6, p=0.020). Endurance of the left leg was associated with LAEF (r=0.79, p=0.001) in patients with HFrEF.

Conclusion

LAS/LAEF are potential cardiac markers in demonstrating the link between cardiac and peripheral limitations of exercise capacity. Thus, integrating LAS/LAEF in the evaluation of exercise intolerance in patients with HF could be useful.

Funding Acknowledgement

Type of funding sources: None.
Clinical course and related costs of patients with diabetes and heart failure and/or chronic kidney disease, drawn from a sample of more than 7 million people
Authors: Maggioni A.P , Piccinni C , Calabria S , Dondi L , Ronconi G , Martini N
Published: October 2021

Background

Diabetes (T2DM), heart failure (HF) and chronic kidney disease (CKD) are among the leading causes of mortality and hospitalization worldwide. This analysis of the Ricerca e Salute (ReS) database is aimed to describe clinical epidemiology, 2-year outcomes and direct costs of T2DM patients with HF, CKD or both in a community setting.

Methods

Analyses were performed on the ReS database including 7,365,716 subjects. During 2015, subjects with T2DM were selected and subsequently split in the following mutually exclusive cohorts (Figure):

– “healthy” T2DM patients, subjects with T2DM but without coronary artery disease (CAD), HF, stroke, TIAs, peripheral artery disease (PAD) and CKD.

– Patients affected by T2DM and HF.

– Patients affected by T2DM and CKD.

– Patients affected by T2DM and both HF and CKD.

Results

Table shows the baseline characteristics, hospitalization reasons, and related costs of the 4 cohorts. In the 2-year follow-up, T2DM patients with comorbidities are older, more frequently males, and more often admitted for CV and renal reasons. T2DM patients with both HF and CKD have the worst outcome profile. The cost per patient per year is 5 times more for T2DM patients with both HF and CKD than for those with T2DM without these comorbidities.

Conclusions

Coexistence of HF and/or CKD in patients with T2DM ia associated with a very high clinical and economical burden. Instead of treating each condition individually, the most appropriate approach should be to adopt a collaborative approach that embraces CV, renal and metabolic diseases.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): This research was partially supported by an unrestricted grant from Astra Zeneca. Astra Zeneca was not involved in data collection, analysis and interpretation, in writing the report, nor in deciding to submit the article for publication.
Is heart failure associated with worse outcomes in patients admitted with pneumonia – nationwide analysis
Authors: Arif A W , Murthi M , Mehdi S A , Yadav N
Published: October 2021

Background

Heart failure (HF) constitutes a huge public health burden today with acute respiratory infections being among the main precipitating causes for hospitalization. On the other hand, HF is a known risk factor for pneumonia which is the most common cause of adult hospital admissions in the United States.

Objective

To examine the effect of HF on the in-hospital outcomes of pneumonia

Methods

The National Inpatient Sample (NIS) database, 2016–2018, was queried for inpatient principal diagnosis of all-cause pneumonia, and the study group was stratified into those with and without HF as a secondary diagnosis, using International Classification of Diseases-10 (ICD-10) codes. Multivariate logistic and linear regression analyses were used to adjust for confounding. Stata 16 software was used for data analysis.

Results

1,929,598 adults were hospitalized with the primary diagnosis of pneumonia, of which 499,740 (25.9%) had HF. The incidence of mortality was 4.2% (n=20,785) in those with HF compared to 2.0% (n=28,365) in those without HF. The adjusted odds ratio (aOR) of inpatient mortality for pneumonia patients with HF compared to those without HF was 1.35 (95% CI, 1.29–1.42; p<0.001) when adjusted for patient demographics, comorbidities, and hospital characteristics. The adjusted hospital length of stay (LOS) in pneumonia patients with HF as compared to those without HF (mean difference= +1.40 days, p<0.001) was significantly longer. Complications such as arrhythmias (aOR=3.18; 95% CI, 3.12–3.25; p<0.001), acute hypoxic respiratory failure (aOR=1.26; 95% CI, 1.24–1.29; p<0.001), acute kidney injury (aOR=1.34; 95% CI, 1.31–1.37; p<0.001), septic shock (aOR=1.60; 95% CI, 1.41–1.81; p<0.001), cardiogenic shock (aOR=7.40; 95% CI, 5.65–9.65; p<0.001) and cardiac arrest (aOR=1.91; 95% CI, 1.71–2.14; p<0.001) were more common in pneumonia patients with HF than those without HF.

Conclusion

In patients hospitalized for pneumonia, HF is associated with increased odds of inpatient mortality and longer LOS. Complications such as arrhythmias, acute hypoxic respiratory failure, acute kidney injury, septic shock, cardiogenic shock and cardiac arrest occur more frequently in pneumonia patients with HF.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Relationship of early intensive- or coronary care unit admission and post-discharge performance of activities of daily living in patients with acute decompensated heart failure
Authors: Kanda M , Tateishi K , Nakagomi A , Iwahana T , Okada S , Kuwabara H , Kobayashi Y , Inoue T
Published: October 2021

Background

The management of acute decompensated heart failure (ADHF) often requires intensive care. However, the effects of early intensive care unit (ICU)/coronary care unit (CCU) admission on activities of daily living (ADL) in ADHF patients have not been precisely evaluated. Thus, we assessed whether early ICU entry can improve post-discharge ADL performance in these patients.

Methods and results

ADHF patients (New York Heart Association I–III) admitted on emergency between April 1, 2014, and December 31, 2018, were selected from the Diagnosis Procedure Combination database and divided into ICU/CCU (ICU) and general ward (GW) groups according to the hospitalization type on admission day 1. The propensity score was calculated to create matched cohorts where treatment assignment (ICU/CCU admission) is independent of measured baseline confounding factors including ADL at admission. The primary outcome was post-ADL defined according to the Barthel index (BI) at discharge. Secondary outcomes included length of stay (LOS) and total hospitalization cost (expense). Overall, 12,231 patients were eligible, and propensity score matching created 2,985 pairs. After matching, post-ADL was significantly higher in the ICU group (GW 71.5±35.3 vs. ICU 78.2±31.2, P<0.001, difference in mean 6.7 (95% CI 5.1–8.4) points). After matching, LOS was significantly shorter and expenses were significantly higher in the ICU group. Subanalyses showed that patients with low ADL at admission (BI<60) mainly benefited from early ICU/CCU entry.

Conclusions

Early ICU/CCU entry was beneficially associated with post-ADL in patients with emergency ADHF admission. ADL at admission might serve as a useful criterion for ICU admission.

Funding Acknowledgement

Type of funding sources: None.
CA 125 in the diagnosis and risk stratification of acute heart failure
Authors: Wussler D , Bayes-Genis A , Belkin M , Strebel I , Kozhuharov N , Revuelta-Lopez E , Nowak A , Lupon J , Gualandro D M , Shrestha S , Breidthardt T , Nunez J , Mueller C ,   Cardiovascular Research Institute Basel
Published: October 2021

Background

Recent evidence confirms the elevation of CA 125 in non-tumor processes such as acute heart failure (AHF). However, the utility of this novel biomarker for diagnosis, prognosis, and therapy guidance in AHF remains unclear.

Purpose

To investigate the potential of CA 125 for diagnosis, prognosis and therapy guidance in unselected AHF patients presenting with acute dyspnea to the emergency department (ED).

Methods

We quantified CA 125 in a blinded fashion among patients presenting with acute dyspnea to the ED in a multicenter diagnostic study. Final diagnosis of AHF including AHF-phenotype was centrally adjudicated by two independent cardiologists. To further characterize CA 125's potential in AHF correlations with established biochemical and imaging markers were assessed. Diagnostic accuracy for AHF was quantified by the area under the receiver operating characteristic curve (AUC). All-cause mortality within 360 days was the prognostic endpoint.

Results

Among 470 patients eligible for this analysis, 268 (57.0%) had adjudicated AHF. CA 125 concentrations at presentation were significantly higher among AHF patients vs. patients with other final diagnoses (45.8 U/ml [interquartile range (IQR), 18.5–110.3] vs. 16.2 U/ml [IQR, 9.6–31.6], p<.001). Patients with worsening heart failure had significant higher CA 125 levels compared to other heart failure phenotypes (p=.018). There was a significant positive correlation of CA 125 and high-sensitivity cardiac troponin T and NTproBNP and a significant negative correlation of CA 125 and left ventricular ejection fraction (correlation coefficients 0.204, 0.220, −0.331, respectively; all ps<.001). CA 125's AUC for AHF was significantly lower compared to NTproBNP's in the overall population (0.72, 95% confidence interval (CI) 0.67–0.76 vs. 0.93, 95% CI 0.90–0.95, p<.001, Figure 1) and in predefined subgroups according to age, gender and renal function. Among 268 AHF patients, 84 (31.3%) died within 360 days of follow-up. CA 125 plasma concentrations above the median indicated increased risk of all-cause mortality (hazard ratio 2.06, 95% CI 1.31–3.24; p=.002, Figure 2). CA 125's prognostic accuracy for 360-days mortality was comparable with NT-proBNP's and high-sensitivity cardiac troponin T's. CA 125 did not independently predict all-cause mortality at 360 days when used in validated multivariable regression models and had no interactions with medical therapies at discharge.

Conclusion

CA 125 may aid physicians in the risk stratification and rapid triage of patients with suspected AHF.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation Figure 1. ROC curve comparisonFigure 2. Kaplan-Meier curve 360 days mortality
Impact of cardiac rhythm abnormality on hospital outcomes of patients with hypertrophic cardiomyopathy
Authors: Shah K , Thyagaturu H , Harmouch F , Gandhi H , Mughal M , Modi V , Kothari J , Shirani J
Published: October 2021

Background

Serious cardiac arrhythmias [atrial fibrillation/flutter (AFF), and ventricular tachycardia/fibrillation (VTF)] are associated with adverse outcomes in general population of patients with hypertrophic cardiomyopathy (HCM).

Purpose

We aimed to evaluate the impact of such rhythm abnormalities on in-hospital outcomes of adults with HCM.

Methods

The National Inpatient Sample reported 45,305 admissions for adults with HCM during a two-year period (2016–2017). Among them, 21,220 patients (47%) also had AFF and/or VTF. Baseline characteristics and in-hospital outcomes of the two groups were compared. Multivariable logistic regression analysis was used to assess the independent impact of rhythm abnormalities on in-hospital outcomes of HCM patients.

Results

HCM patients with arrhythmias were older (68±26 vs 64±29 years), were more often male (43% vs 36%), and had higher prevalence of congestive heart failure (45% vs 28%), chronic kidney disease (27% vs 22%), hyperlipidemia (52% vs 48%), obstructive sleep apnea (17% vs 13%), chronic obstructive pulmonary disease (22% vs 18%) and thyroid disease (19% vs 16%) [Table 1, all p<0.001]. Hospital mortality was significantly higher among those with arrhythmias (4.7% vs 2.7%, p<0.05). Multivariate logistic regression analysis identified arrhythmias as an independent predictor of in-hospital mortality (adjusted odds ratio=1.51, 95% confidence interval=1.19–1.91, p=0.001), increased mean length of stay (Δ +0.75 days, p<0.001) and increased mean total hospital cost (Δ +$18,263, p<0.001).

Conclusion

Adults with HCM and AFF and/or VTF are older and have higher prevalence of comorbid conditions. Presence of such rhythm abnormalities is an independent predictor of higher mortality, length of stay and total cost in HCM adults admitted to hospital.

Funding Acknowledgement

Type of funding sources: None. Table 1
Machine learning to aid in the diagnosis of acute heart failure in the emergency department
Authors: Doudesis D , Lee K K , Anwar M , Astengo F , Newby D , Japp A , Tsanas A , Shah A , Richards M , McMurray J , Mueller C , Januzzi J , Mills N ,   CoDE-HF investigators
Published: October 2021

Background

B-type natriuretic peptide (BNP) and mid-regional pro-atrial natriuretic peptide (MRproANP) testing are recommended to aid in the diagnosis of acute heart failure. However, the application of these biomarkers for optimal diagnostic performance is uncertain.

Methods

We performed a systematic review and harmonised individual patient-level data to evaluate the diagnostic performance of BNP and MRproANP for the diagnosis of acute heart failure using random-effects meta-analysis. We subsequently developed and externally validated a decision-support tool called CoDE-HF for both BNP and MRproANP that combines the natriuretic peptide concentrations with clinical variables using machine learning to report the probability of acute heart failure for an individual patient.

Results

Fourteen studies from 12 countries provided individual patient-level data in 8,493 patients for BNP and 3,847 patients for MRproANP, in whom, 48.3% (4,105/8,493) and 41.3% (1,611/3899) had an adjudicated diagnosis of acute heart failure, respectively. The negative and positive predictive values of guideline-recommended thresholds for BNP (100 pg/mL) and MR-proANP (120 pg/mL) were 93.6% (95% confidence interval 88.4–96.6%) and 68.8% (62.9–74.2%), and 95.6% (92.2–97.6%) and 64.8% (56.3–72.5%), respectively. However, we observed significant heterogeneity in the diagnostic performance across important patient subgroups (Figure 1). In the external validation cohort, CoDE-HF was well calibrated with excellent discrimination in those without prior acute heart failure for both BNP and MRproANP (area under the curve of 0.946 [0.933–0.958] and 0.943 [0.921–0.964], and Brier scores of 0.105 and 0.073, respectively). CoDE-HF performed consistently across all subgroups for both BNP and MRproANP, and identified 30% and 65.7% at low-probability (negative predictive value of 99.1% [98.8–99.3%] and 99.1% [98.8–99.4%]), and 30% and 17.3% at high-probability (positive predictive value of 91.3% [90.7–91.9%] and 70.0% [68.5–71.4%]) in those without prior heart failure, respectively (Figure 2).

Conclusion

In an international collaborative analysis, we observed that guideline-recommended thresholds for BNP and MRproANP to diagnose acute heart failure varied significantly across patient subgroups. A decision-support tool using machine learning to combine natriuretic peptides as a continuous measure and other clinical variables provides a more accurate and individualised approach.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Medical Research Council and British Heart Foundation Figure 1. NPV of BNP threshold (100 pg/mL)Figure 2. NPV of the CoDE-HF rule-out score
Dexamethasone in acute cardiopulmonary syndrome with hyperinflammatory state
Authors: Cosmi D , Mariottoni B , D'Orazio S , Angori P , Cosmi F
Published: October 2021

Introduction

Elderly patient hospitalized due to acute heart failure often have a concomitant acute lung disease (acute bronchitis, pneumonia, chronic obstructive pulmonary disease-COPD- exacerbation). Establishing the role of each disease in a clinical picture of acute cardiopulmonary syndrome can be challenging. Procalcitonin has been used as a guide to antibiotic therapy with contrasting results. A common thread of these diseases is inflammation; a hyperinflammatory response determines more serious symptoms and a worse prognosis.

Purpose

We evaluated the effectiveness of a treatment with dexamethasone in patients with acute cardiopulmonary syndrome and a strong inflammatory response.

Materials and methods

We evaluated 157 consecutive HFPEF (heart failure with preserved ejection fraction) patients ≥80 years of age, with concomitant symptoms attributable to acute bronchitis, pneumonia, or COPD exacerbation, hospitalized due to worsening dyspnoea, with an NT-proBNP ≥3,000 pg/ml, and a finding X-ray of lung congestion with or without a consolidation. Reactive C Protein was measured. Patients with SARS-CoV-2, indication to corticosteroids use for other clinical conditions or need for mechanical ventilation were excluded. The 96 patients with values>20 mg/dl were randomized into 2 groups: 48 patients were treated open-label with dexamethasone at a dose of 8 mg iv/day for a maximun of ten days, in addition to the usual therapies for acute heart failure and lung disease, while the same number of patients were treated with the usual therapy. In both groups the antibiotic was administered only if the procalcitonin was≥0.25 μg/L. Clinical recovery time, length of hospitalization, in-hospital mortality, the need for a new hospitalization and mortality at one month were evaluated.

Results

The mean age of the patients was 88±4 years in the dexamethasone group and 87±5 in the usual therapy group. The results are shown in Table 1. Patients treated with dexamethasone experienced a faster clinical recovery and a shorter length of hospitalization. No significant differences were found regarding either in-hospital mortality or need for rehospitalization and mortality at 30 days.

Conclusions

Very elderly patients with acute cardiopulmonary syndrome and hyperinflammatory state associated with an excessive increase in Reactive Protein C have a favorable response to dexamethasone therapy in addition to the usual therapy in terms of clinical improvement and length of hospitalization. Our case history is small to evaluate a possible improvement in mortality. These findings need to be consolidated from double-blind randomized controlled trials

Funding Acknowledgement

Type of funding sources: None. Table 1