bluuebunny/crossref_metadata_2025 huggingface dataset:
Left ventricular end-diastolic pressure predicts in-hospital outcomes in Takotsubo syndrome
Authors: Montone R.A , Del Buono M , Meucci M.C , La Vecchia G , Camilli M , Pedicino D , Trani C , Sanna T , Niccoli G , Crea F
Published: October 2021

Background

Takotsubo syndrome (TTS) is an acute and reversible form of myocardial injury often preceded by an emotional or physical stressful event. Of importance, TTS may be associated to serious adverse in-hospital complications. Coronary angiography and left ventricle angiography remain a cornerstone for TTS diagnosis. However, the prognostic role of invasively assessed left ventricular end-diastolic pressure (LVEDP) at the time of cardiac catheterization has never been investigated.

Purpose

We evaluated the role of invasively assessed LVEDP for predicting in-hospital complications in TTS patients compared to the most widely used echocardiographic parameters of ventricular function.

Methods

We prospectively enrolled 130 patients (mean age 71.2±11.3 years, 114 [87.7%] female) with TTS. Invasive measurement of LVEDP was performed at the time of cardiac catheterization. The rate of in-hospital complications (composite of acute heart failure, cardiogenic shock, life-threatening arrhythmias and all-cause death) was examined.

Results

In-hospital complications occurred in 37 (28.5%) patients. Patients who experienced in-hospital complications had a higher prevalence of neurological trigger and lower prevalence of emotional trigger, higher LVEDP and mean E/e' ratio and lower LV ejection fraction (LVEF) values compared to those who did not experience in-hospital complications. At multivariable Cox regression, higher LVEDP (hazard ratio [HR] 1.12, 95% confidence interval [CI] [1.05–1.20], p<0.001) and lower LVEF (HR 0.95, 95% CI [0.91–0.99], p=0.011) remained independently predictors of in-hospital complications, while emotional trigger was associated to a lower risk (HR 0.24, 95% CI [0.06–0.96], p=0.044). The area under the curve (AUC) for LEVDP in the prediction of in-hospital events was 0.776 (95% CI [0.69–0.86], p<0.001, with a sensitivity and specificity of 95% and 58% using a LVEDP cut-off value of 22.5 mmHg). The AUC was significantly higher for LVEDP than for E/e' ratio (p=0.045).

Conclusions

LVEDP measured at the time of cardiac catheterization may help in identifying TTS patients at higher risk of cardiovascular events during the hospitalization with relevant therapeutic implications. Of note, in the prediction of in-hospital events the LEVDP performed better than non-invasive indexes commonly used for the assessment of diastolic function.

Funding Acknowledgement

Type of funding sources: None.
Clinical impact of pulmonary artery to aorta diameter ratio on left ventricular reverse remodeling in patients with dilated cardiomyopathy
Authors: Shibata N , Hiraiwa H , Kazama S , Kimura Y , Araki T , Mizutani T , Oishi H , Kuwayama T , Kondo T , Morimoto R , Okumura T , Murohara T
Published: October 2021

Background

Left ventricular reverse remodeling (LVRR) is an important predictor for a good prognosis in patients with dilated cardiomyopathy (DCM). Previous reports indicated the pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio as a predictor of adverse outcomes in heart failure patients. However, the impact of the PAD/AoD ratio for predicting LVRR in patients with DCM is unknown.

Aim

The aim of this study is to investigate the association between PAD/AoD ratio and LVRR in patients with DCM.

Methods

From a prospective study, clinically stable DCM patients who were investigated the LVRR on echocardiography and underwent CT at baseline were enrolled. LVRR is defined as left ventricular (LV) ejection fraction increase of 10% and a decrease in indexed LV end-diastolic diameter of 10% compared to those at baseline. PAD and AoD data was collected with nonenhanced computed tomography images at baseline.

Results

In sixty-nine patients (mean age 50.0±13.3 years), the mean LV ejection fraction was 29.8%, and mean LV end-diastolic dimension was 64.5mm, and both of which data was no significant difference between patients with or without LVRR. LVRR was observed in 23 (33.3%) patients. The PAD/AoD ratio was significantly lower in patients with LVRR than without LVRR (81.4% vs. 92.4%, p=0.003). By ROC analysis, the best cut-off for the detection of LVRR was found for a PAD/AoD ratio of 0.9. From multivariate analyses, PAD/AoD ratio was identified as a significant predictor of LVRR. After a median follow-up duration of 2.5 years, the DCM patients with PAD/AoD≥0.9 revealed a significant higher cardiac event than those with PAD/AoD<0.9 (log-rank, p=0.007)

Conclusions

The PAD/AoD ratio is useful for predicting LVRR in patients with DCM. The DCM patients with high PAD/AoD ratio had a poor long-term outcome.

Funding Acknowledgement

Type of funding sources: None. ROC curve for LVRR predictionKaplan-Meier survival curves
Prognostic significance of epicardial adipose tissue in heart failure with preserved and reduced ejection fraction
Authors: Pugliese N.R , De Biase N , Mazzola M , Paneni F , Del Punta L , Gargani L , Mengozzi A , Virdis A , Nesti L , Taddei S , Flammer A , Borlaug B.A , Ruschitzka F , Masi S
Published: October 2021

Background

Increased epicardial adipose tissue (EAT) thickness correlates with metabolic syndrome, insulin resistance, microvascular dysfunction and enhanced pericardial restraint.

Purpose

We measured echocardiographic EAT thickness in heart failure (HF) patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction to determine whether EAT could bear prognostic significance at clinical follow-up.

Methods

We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) referred to our hospital due to dyspnoea and/or effort intolerance. We performed a resting clinical and biohumoral evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. A composite of cardiovascular death and HF-related hospitalization was chosen as endpoint during follow-up.

Results

Patients with HFpEF displayed higher EAT thickness (median 8 mm, interquartile range [IQR] 4–12 mm) than HFrEF (median 3 mm, IQR 2–6 mm; p<0.0001). During a median follow-up of 20.9 months (IQR 15–25 months), we reported 34 cardiovascular deaths and 146 HF hospitalizations, with no significant differences between the two HF subsets. EAT predicted adverse events independently from body mass index and well-established markers of poor prognosis (e.g., NT-proBNP, peak oxygen consumption). The risk of adverse events increased with increasing EAT thickness in HFpEF and with EAT thinning in HFrEF. Kaplan-Meier analyses for the composite endpoint showed that in HFpEF, the survival probability was significantly lower in patients with thicker EAT than those with thinner EAT. In HFrEF, conversely, patients with thicker EAT had a higher survival probability than those with reduced EAT thickness (Figure 1).

Conclusion

EAT accumulation is more marked in HFpEF than HFrEF and carries different prognostic meanings in the two subsets. In HFpEF, EAT thickening portends adverse outcome, which may be due to increased mechanical restraint and secretion of pro-inflammatory and pro-atherogenic adipokines. In HFrEF, greater EAT thickness seems to have a protective role, while EAT thinning is associated with a worse prognosis, likely reflecting a catabolic state (i.e. cardiac cachexia). Larger studies will clarify whether EAT is a bystander or an active player in the different HF phenotypes.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Current use of NT-proBNP in elderly patients and the impact of the selected threshold value: lessons from a big data analysis
Authors: Meune C , Goudot F.X , Boukertouta T , Lazureanu A , Msadek S , Chenevier-Gobeaux C , Martins-Meune E
Published: October 2021

Background

Natriuretic peptides (NPs) are widely used in the diagnosis and risk stratification of heart failure (HF).NPs may have a reduced discriminative ability in the subgroup of elderly patients.

Methods

We examined all biological tests performed from February 2010 to August 2015 in two districts in the French Brittany. We report the “real-world” use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an elderly population and examine the measured concentration and potential impact of the cut-off value's selection.

Results

From a total of 3,606,432 tests ordered in 557,650 adult patients, 56,653 included at least one NT-proBNP measurement. NT-proBNP measurements gradually increased by 10-y age categories up to 80–90 y, and 39,828 (70.3%) of all measurements have been done in patients ≥75y. NT-proBNP concentrations increased with advanced age (Pearson's correlation coefficient: 0.2; p<10–5), with concentrations of 3,564±6,440 ng/L in patients ≥75y. NT-proBNP was inversely correlated with creatinine clearance (p<10–5). Respective proportions of NT-proBNP below the threshold value were 22.6% in patients aged 70 to 80y and less than 10% in those over 80 y when considering a single threshold value of 125 ng/L, and 31% and 33% in the same groups when considering a dual age-adjusted threshold value of 450 ng/L in patients >75y (p<0.001 for all comparisons).

Conclusion

Among a very large cohort, we observed that NT-proBNP is increasingly measured in elderly patients. NT-proBNP concentrations increase with age, and the selection of the threshold value markedly impacts the proportion of “low” versus “high” results.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Roche Diagnostics Proportion (in %) of low NT-proBNP
Proteomic profiling for detection of early-stage heart failure in the community
Authors: Cauwenberghs N , Sabovcik F , Haddad F , Kuznetsova T
Published: October 2021

Background and purpose

Biomarkers may provide insight into the molecular mechanisms underlying cardiac remodelling and dysfunction. Using a targeted proteomic approach, we aimed to identify circulating biomarkers associated with early-stage heart failure and extract a proteome-based risk classifier for this condition.

Methods

575 community-based participants (mean age, 57 years; 51.7% women) underwent echocardiography and proteomic profiling (CVD II panel, Olink Proteomics). We applied partial least squares-discriminant analysis (PLS-DA) and a machine learning algorithm (extreme gradient boosting, XGBoost) to identify key proteins associated with echocardiographic abnormalities. We used Gaussian Mixture modelling for unbiased clustering to construct phenogroups based on influential proteins in PLS-DA and XGBoost.

Results

Of 87 proteins, 13 were important in PLS-DA and XGBoost modelling for detection of left ventricular (LV) remodelling, LV diastolic dysfunction and/or left atrial reservoir dysfunction: placenta growth factor, kidney injury molecule-1, prostasin, angiotensin-converting enzyme-2, galectin-9, cathepsin L1, matrix metalloproteinase-7, TNFR superfamily members 10A, 10B and 11A, interleukins-6 and 16 and alpha-1-microglobulin/bikunin precursor. Based on these proteins, the clustering algorithm divided the cohort into two distinct phenogroups, with each cluster grouping individuals with a similar protein profile. Participants belonging to the second cluster (n=118) were characterized by an unfavourable cardiovascular risk profile and adverse cardiac structure and function. The adjusted risk of presenting cardiac maladaptation was higher in this phenogroup than in the other cluster (P<0.0001).

Conclusion

We identified proteins reflecting renal function, extracellular matrix remodelling, angiogenesis and inflammation to be associated with echocardiographic signs of early-stage heart failure. Focused proteomic phenomapping discriminated individuals at high risk for cardiac maladaptation in the community.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders
Epicardial adipose tissue, cardiovascular hemodynamics and metabolic profile in heart failure with preserved and reduced ejection fraction
Authors: Pugliese N.R , Mazzola M , De Biase N , Paneni F , Del Punta L , Gargani L , Mengozzi A , Virdis A , Nesti L , Taddei S , Flammer A , Borlaug B.A , Ruschitzka F , Masi S
Published: October 2021

Background

Epicardial adipose tissue (EAT) acts as a paracrine organ and could exert direct mechanical compression on the myocardium.

Purpose

We investigated the impact of echocardiographic EAT thickness on metabolic profile and cardiovascular hemodynamics at rest and during exercise in heart failure (HF) patients with reduced (HFrEF) and preserved (HFpEF) ejection fraction

Methods

We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) referred to the our hospital due to dyspnoea and/or effort intolerance. We performed a resting clinical and biohumoral evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. The protocol also included 44 healthy controls.

Results

Patients with HFpEF displayed the greatest EAT thickness (median 8 mm, interquartile range [IQR] 4–12 mm), while those with HFrEF had thinner EAT (median 3 mm, IQR 2–6 mm) than controls (median 5 mm, IQR 3–7 mm; p<0.0001). In HFrEF, EAT thickness was inversely associated with natriuretic peptides, Troponin T, and C-reactive protein levels. In HFpEF, it was directly correlated with Troponin-T and C-reactive protein levels. EAT thickness was inversely correlated with peak oxygen consumption (VO2) and peripheral oxygen extraction (AVO2diff) in HFpEF, while a direct association was observed in HFrEF (Fig 1). EAT resulted in an independent predictor of peak VO2 and AVO2diff in HFrEF and HFpEF regardless of body mass index, but the relationships were direct in HFrEF (standard regression coefficient [SRC] for peak VO2: 0.18, p=0.02; SRC for peak AVO2diff: 0.17, p=0.03) and indirect in HFpEF (SRC for peak VO2: −0.33, p<0.0001; SRC for peak AVO2diff: −0.25, p<0.0001).

The analysis of cardiac mechanics revealed that thinner EAT was associated with worse left ventricle systolic dysfunction (average S') and remodeling (3D left ventricle mass) in HFrEF. In HFpEF, increased EAT was related to more severe left atrio-ventricular (left atrium reservoir strain/left ventricle global longitudinal strain) and right ventriculo-arterial (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) coupling (Figure 2).

Conclusion

In HFpEF, EAT accumulation is associated with worse hemodynamic and metabolic profile. In HFrEF, conversely, EAT thinning portends more severe LV dysfunction and impaired global functional capacity.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Differences in left ventricular twisting and different strains in patients with heart failure with preserved ejection fraction versus patients with arterial hypertension
Authors: Chilingaryan A , Tunyan L.G , Asatryan A.A , Tumasyan L.R , Kzhdryan H.K , Zelveyan P.H
Published: October 2021

Patients with advanced arterial hypertension (HPT) without heart failure often have left ventricular (LV) changes similar to hypertensive patients with heart failure with preserved ejection fraction (HFpEF). We assumed that cardiac mechanics may be different in both groups.

Methods

We study 58 patients (23 female) with HPT and with left ventricular concentric hypertrophy (LVH) as well as negative diastolic stress test and 52 HPT patients (29 female) with HFpEF NYHA II-III 72±5 years. All patients where in sinus rhythm. HPT and HFpEF patients has comparable degree of LV mass index (LVMI 85.3±8.6 g/m2 vs 86.2±8.9 g/m2, P=NS). Incidence of diabetes mellitus, chronic kidney disease or chronic obstructive lung disease was comparable between groups. 43 sex and age matched healthy subjects served as control (C). Comprehensive 2D/3D echocardiography (EchoCG) with offline measurements of longitudinal (LS), circumferential (CS) and radial strain (RS) global values of entire walls and 3 myocardial layers, LV twist (LVT)was performed before and after symptom limited or heart rate of 120 bpm limited diastolic stress test.

Results

HPT and HFpEF patients had significantly lower absolute values LS, CS, AS, as well as lower values of RS, and LVT compared with controls at rest and after stress test. The values of LS, RS and LVT did not significantly differ at rest in HPT patients and HFpEF patients, but HFpEF patients had lower values of global CS (GCS) due to reduction only in endocardial layer CS (ECS) (LS: 16.4±5.2% vs 16,8±5.9, p=0.07; ECS: 10.9±2,3% vs 17.3±4.1%, p<0.01; GCS: 12.8±3.5% vs 15.1±2.1%, p<0.03; RS: 29.7±10.2% vs 31.1±12.4%, p=0.06; LVT: 2.3±1.4deg vs 2.6±1.7deg, p=0.06). After diastolic stress test patients with HFpEF had significantly lower values of LVT and GCS compared with HPT patients (LVT: 1.8±0.9deg vs 3.4±1.8deg, p<0.001; GCS: 10.4±2.7% vs 17.1±3.4%, p<0.01). We also found greater relative increase (RI) in endocardial LS and LVT in patients with HPT after stress test compared with HFpEF patients, RI of other parameters did not differ between these two groups (RI ELS: 16±2.1% vs 10.5±1,7%, p<0.03; RI LVT 33.3±6,4% vs −21.7±4.1%, p<0.0001). ECS had the diagnostic value to predict HFpEF (area under curve 0.874), RI LVT was the best predictor of HFpEF symptoms (area under curve 0.912) with cut off value 22.3%.

Conclusion

ECS is reduced in HFpEF patients compared with HPT patients with the same degree of structural abnormalities on conventional EchoCG and is a predictor of HFpEF. HPT patients have more relative improvement in ELS during stress test compared with HFpEF patients. RI LVT was the best predictor of HFpEF symptoms.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): City Hall resources
Left atrial coupling index versus left atrial function index in heart failure with reduced ejection fraction and iron deficiency
Authors: Tsarouchas A , Bakogiannis C , Mouselimis D , Pagourelias E.D , Kelemanis I , Boulmpou A , Vergopoulos S , Vassilikou A , Tzikas S , Fragakis N , Papadopoulos C.E , Vassilikos V.P
Published: October 2021

Background

Left atrial (LA) form and function has been the focus of extensive research in heart failure with reduced ejection fraction (HFrEF). The LA coupling index (LACI, see Picture 1 for definition) and the LA function Index (LAFI) have both been proposed as potent predictors of morbidity and mortality in HFrEF. Albeit promising, both parameters have drawbacks that could limit their usefulness in clinical settings - LACI can only be measured during sinus rhythm (SR), while LAFI calculation is arguably more involved. A side-by-side comparison of the two indices has not yet been performed.

Purpose

Investigate and compare the feasibility and efficacy of using LACI and LAFI as prognostic factors in HFrEF.

Methods

HFrEF patients that visited our outpatient HF clinic were invited to participate in the study. Clinical examination, 6-minute walk testing, and a full echocardiographic study were performed, the latter enabling quantification of LACI, LAFI, as well as most traditional echocardiographic predictors of HF prognosis (Picture 1). LACI and LAFI cut-offs of 6 and 25 respectively were defined in accordance with the relevant literature. Cox regression was performed to assess each parameter's correlation with risk of HF-related hospitalization and mortality over a 6-month follow-up period.

Results

In the end, 63 patients were included in the study (aged 69.3±9.7 years, 84% male). LACI could not be measured in 19 patients due to atrial tachycardia. The median LACI was 6.2 (8.7) while the median LAFI of the entire sample was 24.8 (44.5). LACI and LAFI correlated strongly (r=−0.813, p<0.001). Neither correlated significantly with the risk of HF-related hospitalization (Picture 1) or death in our sample (Picture 2). 6MWD was the only parameter to independently correlate with increased risk of hospitalization (HR=0.39, p<0.001) or death (HR=0.42, p=0.02).

Conclusions

The collinearity detected between LACI and LAFI indicate that both quantify similar aspects of left atrial (dys)function. That said, neither index had significant capability to predict hospitalization or death in our sample of HFrEF patients. Although a non-significant trend for higher LACI in patients with poorer prognosis was detected in our sample, it was also incalculable in 30% of patients, who were not in SR during echocardiography. Extended follow-up of an expanded sample size will enable more refined investigation of LACI's and LAFI's prognostic capacity.

Funding Acknowledgement

Type of funding sources: None. Hospitalization Cox regression resultsLACI and LAFI survival curves
Outcomes of remote pulmonary artery hemodynamic monitoring in heart failure patients with obstructive sleep apnea
Authors: Oberoi M , Rajpurohit N , Petrasko M , Stys A , Stys T , Vicinsky D , Jonsson O
Published: October 2021

Introduction

Obstructive sleep apnea (OSA) is often associated with heart failure (HF). Remote pulmonary artery (PA) hemodynamic monitoring has shown to decrease HF related readmissions. However, there is paucity of data regarding its efficacy and mortality in patients with OSA.

Purpose

Real-world analysis of outcomes of remote PA hemodynamic monitoring using CardioMEMS device in reducing HF hospitalization in patients with OSA [apnea–hypopnea index (AHI) ≥5].

Methods

Retrospective data was collected for patients with HF who had CardioMEMS device implanted based on FDA indications from April 2015 to August 2020. The number of hospitalizations, emergency department (ED) and HF clinic visits data was collected for 1-year pre and 1-year post device implantation. Mortality data was also collected at 1-year post-implantation. Patients who were diagnosed with OSA based on AHI ≥5 on sleep study at the time of implantation were included in the study. Analysis was done using Kruskal-Wallis test for comparison between heart failure patients with and without OSA. Mortality was compared with Pearson's chi-squared test.

Results

CardioMEMS device was implanted in 177 patients during the study period. Of this population, 108 (61%) patients had known OSA at the time of implantation. There was a statistically significant decrease in overall mean HF admissions from 1.80 (± 1.55) to 0.62 (± 1.07), 65.6%, p<0.001 and mean HF ED visits from 1.37 (± 1.50) to 0.5 (± 0.95), 63.5%, p<0.001 in 1-year pre- and post-implantation among OSA patients. When comparing outcomes between HF patients with and without OSA, there was no statistically significant difference observed between them in all-cause admissions, HF admissions, ED visits, ED HF visits, and HF clinic visits 1-year pre and post implantation. Also, no statistically significant difference was observed in mortality between the groups at 1-year post-implantation.

Conclusions

PA hemodynamic monitoring using CardioMEMS device had a net benefit in reducing HF admissions and HF ED visits in OSA patients which was similar in patients without OSA.

Funding Acknowledgement

Type of funding sources: None.
Prognostic significance of anemia in women with suspected ischemia, an insight from the women ischemia syndrome evaluation study (WISE)
Authors: Asif A , Lauzon M , Sopko G , Bittner V , Reis S , Handberg E , Pepine C J , Mankad S , Bairey Merz N
Published: October 2021

Background

Anemia is associated with adverse cardiovascular outcomes in patients with myocardial infarction and congestive heart failure. Anemia is more prevalent in women. We investigated the prognosis of anemia in women with suspected ischemic heart disease.

Purpose

To study if hemoglobin levels at baseline in women with symptoms of ischemia predicts long term all-cause mortality and major adverse cardiac events.

Methods

We studied 885 women enrolled in WISE (1997–2001) undergoing clinically indicated coronary angiography for suspected ischemia. Anemia was defined as hemoglobin (Hb) level <12g/dL. Major adverse cardiovascular event (MACE) included all-cause death, nonfatal myocardial infarction, stroke and heart failure hospitalization. Cox regression models and Kaplan-Meier methods were was used.

Results

Overall, 885 women, mean age 58.4±11.7 years, 21.1% and anemia were followed for 6.8 years. Anemic women had higher creatinine, history of diabetes mellitus, hypertension and CHF (p<0.05), but not obstructive coronary artery disease compared to non-anemia women (p=0.97). Anemic women had higher all-cause mortality and MACE (Figure). In multivariate analysis, anemia was independently associated with increased MACE risk (hazard ratio (HR): 1.5, 95% confidence interval [1.11- 2.01, p=0.007]) but not all-cause mortality (HR: 1.2 [0.84–1.72, p=0.30]).

Conclusions

Among women evaluated for symptoms of ischemia, anemia is associated with and independently predicts MACE. Further research targeting anemia treatment in women to mitigate these adverse outcomes is warranted.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): NIH USA
Sex-dependent impact of coronary microvascular dysfunction on long-term clinical outcomes in patients with no-obstructive coronary artery disease
Authors: Toya T , Ahmad A , Corban M T , Sara J D , Ozcan I , Lerman L O , Lerman A
Published: October 2021

Background

Coronary vasomotor response is different between males and females. However, the prognostic impact of this difference in coronary physiologic indices has not been characterized in patients with no obstructive coronary artery disease (NOCAD).

Purpose

We aimed to investigate the sex-specific differences of coronary vasomotor function in response to adenosine in a large cohort of patients with NOCAD and its impact on long-term clinical outcomes

Methods

We included 668 NOCAD patients who underwent invasive coronary vasoreactivity testing using intracoronary incremental doses of adenosine (18–72 μg) with available follow-up data. Indices of coronary vasomotor response were compared between males and females, and their prognostic impact on major adverse cardiovascular events (MACE: death, myocardial infarction, revascularization, and stroke) were analyzed based on sex.

Results

Females (N=461, mean age 54±12 years) had lower baseline microvascular resistance (BMR) and higher baseline average peak velocity (APV) than males (N=207, mean age 53±13 years), while hyperemic microvascular resistance (HMR) and hyperemic APV were similar between males and females. Consequently, coronary flow reserve (CFR: hyperemic/baseline APV) and resistive reserve ratio (RRR: BMR/HMR) were lower in females than males (Figure 1A). Lower CFR and RRR, as well as lower BMR and higher baseline APV were associated with MACE only in males, but not in females. Higher HMR was the only predictor for MACE in females (Figure 1B).

Conclusions

Sex-specific differences in coronary vasomotor response to adenosine may provide different prognostic values between males and females.

Funding Acknowledgement

Type of funding sources: None.
Impact of previous cardiac conditions in prognosis and clinical management of patient with COVID-19 infection
Authors: Antonana S , Monteagudo J M , Arteagoitia A , Gonzalez A , Ortega R , Rivas S , Martinez-Moya R R , Sanroman M A , Lorente-Ros A , Rincon L M , Zamorano J L
Published: October 2021

Background

Recent studies suggest a higher mortality rate because of COVID-19 in patients with previous cardiac conditions compared to those without. Given the limited resources of intensive care units (ICU) during the pandemic outbreak, this fact has important implications.

Purpose

The main purpose of this study was to compare the 30-day mortality of the COVID-19 infection in patients with and without previous cardiac conditions. The secondary end point was to assess the differences in clinical severity of the infection (as development of Acute Respiratory Distress Syndrome – ARDS) and ICU admission amongst these patients.

Methods

A total of 1708 consecutive patients were prospectively included. The inclusion criteria were: a confirmed positive diagnosis of COVID-19 infection by PCR and being admitted to our centre between 18th and 23rd March 2020 and 22nd August and 9th January 2021. Patients were classified in two groups according to the presence of previous cardiac conditions (defined as previous history of myocardial infarction, heart failure and atrial fibrillation). Other comorbidities were extensively explored and Charlson Comorbidity Index was calculated. A propensity-score matching was performed and 145 patients with previous cardiac conditions were matched with 145 patients without.

Results

The group of patients with a previous cardiac condition included 421 patients (24.6%). The crude analysis showed a higher 30-day mortality rate among patients with previous cardiac affections (35.6% vs. 14.6%, p<0.001). They were also less likely to be admitted to the ICU (9.8% vs. 6.2%, p=0.022) and had a higher prevalence ARDS (48.9% vs. 33.9%, p<0.001). In the matched cohort, there were no significant differences between both groups regarding mortality (24.8% in the group of patients with previous cardiac conditions vs. 31.0%, p=0.272) nor ARDS prevalence (50.3% vs. 53.1%, p=0.655). There was a trend toward patients with previous cardiac conditions to be less likely to be admitted to the ICU (4.8% vs. 9.7%, p=0.090).

Conclusions

Patients with a personal history of previous cardiac conditions were less likely to be admitted to the ICU. However, our results show that when comparing cohorts with similar comorbidity burden, a previous cardiopathy “per se” does not significantly increase the risk of death in patients with a concomitant COVID infection.

Funding Acknowledgement

Type of funding sources: None. Mortality unmatched vs matched cohort
Comparison of in-hospital outcomes and 30-days readmissions between type 1 and type 2 myocardial infarction patients: a study of the nationwide readmissions database
Authors: Wu L , Song D D , Daibes J A , Das S , Pena M K , Tamis-Holland J
Published: October 2021

Introduction

Traditionally Type- 1 myocardial infarction (T1-MI) results from a plaque erosion, rupture, or fissure. In contrast, Type- 2 myocardial infarction (T2-MI) is a consequence of severe supply and demand mismatch. Despite the different mechanisms, both T1-MI and T2-MI can be associated with severe morbidity and mortality. Yet there is sparse data analyzing in-hospital outcomes and readmission rates comparing patients who present with T1-MI and T2-MI.

Purpose

We aimed to compare the outcome data of patients with T1-MI and T2-MI derived from the Nationwide Readmissions Database, a large national database of hospital readmissions.

Method

We utilized the 2018 Nationwide Readmissions Database to identify all index hospital admissions with a primary diagnosis of “acute MI” (AMI) using ICD-10 diagnosis codes. All AMI admissions were further categorized into ST-elevation myocardial infarction (STEMI), no-ST-elevation myocardial infarction (NSTEMI), or T2-MI. Primary outcomes analyzed included 30-days major adverse cardiovascular events (MACE) (defined as re-infarction, repeat revascularization and death within 30 days of admission), short term mortality and readmission rates.

Results

Among 556,816 total admissions for AMI, 28,250 (5.1%) were T2-MI. Table 1 compares baseline variables and short-term outcomes for patients with T1-MI vs T2-MI. Compared to patients with T1-MI patients with T2-MI were older, more likely to be female, and had a higher burden of comorbidities. Additionally, T2-MI patients were less likely to receive coronary revascularization during the index admission. The mean length of stay for T2-MI patients was 4.7±0.6 days, which is longer than the length of stay for STEMI patient (4.1±0.4 days) but slightly shorter than NSTEMI patient (4.9±0.4 days). T2-MI patients had a higher rate of all-cause 30-days readmissions but a lower rate of 30-days MACE. Early mortality rate (within 30 days of index admission) in T2-MI patients was comparable to NSTEMI patients but was lower than STEMI patients. Cox proportional-hazards model adjusting for age, sex, comorbidities and type of hospital setting demonstrated that T2-MI was associated with a lower 30-day MACE risk (T2-MI vs STEMI: [HR 0.33 (95% CI 0.31–0.36)]; T2-MI vs NSTEMI [HR 0.70 (95% CI 0.64–0.75)]) and a lower risk of early mortality (T2-MI vs STEMI: [HR 0.29 (95% CI 0.26–0.32)]; T2-MI vs NSTEMI [HR 0.71 (95% CI 0.65–0.79)]). The adjusted HR for 30-days all-cause readmissions was higher with T2-MI, (T2-MI vs STEMI: [HR 1.16 (95% CI 1.10–1.23)]; T2-MI vs NSTEMI: [HR 1.11 (95% CI 1.06–1.16)]).

Conclusion

T2-MI patients are older and have a higher burden of comorbidities. After adjusting for baseline comorbidities, all-cause readmission risk is higher in T2-MI but short-term MACE and mortality is lower with T2-MI.

Funding Acknowledgement

Type of funding sources: None.
Machine learning aids clinical decision making in patients presenting with angina and non-obstructive coronary artery disease
Authors: Ahmad A , Shelly Cohen M , Corban M T , Murphree Jr D H , Toya T , Sara J D , Ozcan I , Lerman L O , Friedman P A , Attia Z I , Lerman A
Published: October 2021

Background

Coronary microvascular dysfunction (CMD) is associated with an increased risk of cardiovascular morbidity and mortality. The current gold-standard comprehensive assessment of CMD is through a limited-access invasive catheterization lab procedure.

Purposes

We aimed to develop a point-of-care tool to assist clinical guidance in patients presenting with chest pain and/or an abnormal functional stress test and with non-obstructive coronary artery disease (NOCAD) based on demographic data and resting ECG waveforms.

Methods

This study included 1,893 NOCAD patients (<50% angiographic stenosis) who underwent CMD evaluation as well as a standard ECG up to 1 year prior. Microvascular endothelial-independent dysfunction was defined by abnormal coronary flow reserve (CFR) <2.5 in response to intracoronary adenosine administration. Microvascular endothelial dysfunction was defined by a maximal percent increase in coronary blood flow (%ΔCBF) ≤50% in response to intracoronary acetylcholine infusion. We trained algorithms to distinguish between the following outcomes: CFR ≤2.5, ΔCBF (%) ≤50, and the combination of both. Two classes of algorithms were trained, one depending on ECG waveforms as input, and another using tabular style clinical data. The optimal classification threshold was determined by maximizing Youden's J.

Results

Mean age was 51±12 years and 66% were females (n=1,257). AUC values ranged from 0.49 to 0.67 for all the outcomes. The best performance in our analysis was for the outcome CFR ≤2.5 via logistic regression on tabular variables. AUC and accuracy were 0.67 and 60%; while sensitivity and NPV were 70% and 85%. Specificity and PPV were 56% and 0.35%. When decreasing the threshold from the “optimal” one (24%) to 15%, sensitivity and NPV increased to 92% and 90% respectively, while specificity and PPV decreased to 25% and 29% respectively (Figure 2).

Conclusion

An AI-enabled algorithm may be able to assist clinical guidance by ruling out CMD in patients presenting with chest pain and/or an abnormal functional stress test. This algorithm needs to be prospectively validated in different cohorts.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The James Nutter Family & Maria Long Family Fellowship in Cardiovascular Research and Mayo Clinic Figure 1Figure 2
Troponin to risk stratify patients with suspected acute coronary syndrome for computed tomography coronary angiography
Authors: Lee K , Bularga A , O'Brien R , Ferry A , Doudesis D , Fujisawa T , Stewart S , Wereski R , Cranley D , Van Beek E , Lowe D , Newby D E , Williams M C , Gray A J , Mills N L
Published: October 2021

Background

Patients with suspected acute coronary syndrome in whom myocardial infarction has been ruled-out are at risk of future adverse cardiac events. However, the optimal approach to risk stratify and investigate these patients is uncertain.

Methods

We performed a prospective cohort study of 250 patients presenting to the Emergency Department with suspected acute coronary syndrome and troponin concentrations below the sex-specific 99th centile (16 ng/L for women and 34 ng/L for men). Patients were recruited in a 2:1 fashion stratified by peak high-sensitivity cardiac troponin I concentration above and below the early rule-out threshold of 5 ng/L (167 patients with intermediate troponin concentrations between 5 ng/L and the sex-specific 99th centile threshold and 83 patients with troponin concentrations <5 ng/L). All patients underwent computed tomography coronary angiography after they were discharged from hospital.

Results

Overall, 37.6% (94/250) of patients had normal coronary arteries whilst 36.0% (90/250) and 26.4% (66/250) had non-obstructive and obstructive coronary artery disease, respectively. Patients with intermediate troponin concentrations were more likely to have coronary artery disease than those with troponin concentrations <5 ng/L (71.9% [120/167] versus 43.4% [36/83]; odds ratio 3.33 [95% confidence interval 1.92–5.78]). This association persisted irrespective of whether patients had anginal symptoms. Conversely, there was no difference in the prevalence of coronary artery disease between those with and without anginal symptoms (63.2% [67/106] and versus 61.8% [89/144]; odds ratio 0.92 [0.48–1.76]). The majority of patients found to have coronary artery disease did not have a prior diagnosis and were not on optimal preventative medical therapy prior to undergoing computed tomography coronary angiography (50.8% [61/120] and 61.0% [22/36], versus 61.7% [74/120] and 69.4% [25/36] in patients with intermediate versus low troponin concentrations, respectively).

Conclusions

In patients with suspected acute coronary syndrome who have myocardial infarction ruled out, those with intermediate cardiac troponin concentrations are three-times more likely to have coronary artery disease than those with low troponin concentrations. Conversely anginal symptoms did not discriminate between those with and without coronary artery disease. Further studies are required to determine if targeting computed tomography coronary angiography to those with intermediate cardiac troponin concentrations can improve the use of preventative medical therapies and clinical outcomes.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The British Heart Foundation Odds ratio of coronary artery diseaseCumulative proportion with CAD
Association between non-wire based computational angiography fractional flow reserve treatment threshold and major adverse cardiac events in patients with stable coronary artery disease
Authors: Lam L Y , Leung C K L , Li K Y , Wu M Z , Ren Q W , Li H L , Yu S S Y , Tse Y K , Yu A S Y , Wong P F , Tse H F , Feng Y , Huo Y , Yiu K H
Published: October 2021

Introduction

Despite class IA guideline recommendations, the use of fractional flow reserve (FFR) in guiding percutaneous coronary intervention (PCI) in stable coronary artery disease (CAD) patients remains low due to limitations including the need of guidewire placement and hyperaemic stimulus. A novel non-invasive index, computational pressure-flow dynamics derived FFR (caFFR), was developed for measuring functional myocardial ischemia and overcoming the limitations of FFR. However, the clinical relevance of caFFR remains to be investigated. In the present study, we aim at evaluating the prognostic value of caFFR among stable CAD patients.

Methods

We retrospectively included patients with stable CAD who underwent coronary angiography during 2014–2016 at our center. Based on the caFFR value, patients were considered to be ischemic (caFFR ≤0.8) and non-ischemic (caFFR >0.8). Further, we recombined the patients to form the adherence cohort, where patients were defined as adherent-to-caFFR if they were ischemic with PCI or non-ischemic without PCI, and nonadherent-to-caFFR if they were ischemic without PCI or non-ischemic with PCI. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause mortality, non-fatal myocardial infarction, and any revascularization. Inverse probability of treatment weighting was used to account for treatment selection bias (PCI vs without PCI, or adherent vs non-adherent), and Cox proportional hazard model was used to evaluate the association with MACE.

Results

A total of 1322 patients, 782 patients in the ischemic cohort and 540 patients in the non-ischemic cohort respectively, were included in our analysis. PCI was associated with a lower risk of MACE in the ischemic cohort (hazard ratio [HR] 0.52; 95% confidence interval [CI], 0.34–0.80; P=0.002), but was not associated with MACE in the non-ischemic cohort. In the adherence cohort, adherent-to-caFFR group (n=803) had a lower risk of MACE compared with nonadherent-to-caFFR group (n=566) (HR, 0.61; 95% CI, 0.44–0.85; P=0.003).

Conclusion

Our study is the first to demonstrate the prognostic value of caFFR, a non-wire based assessment of myocardial ischemia, in patients with stable CAD undergoing PCI. These findings support the use of caFFR that bears the potential of a wider adoption compared with wire-based FFR through a reduction in procedure time, risk and costs.

Funding Acknowledgement

Type of funding sources: None. Weighted Kaplan-Meier curvesWeighted Cox proportional hazards model
Discordance between plain coronary angiography and quantitative flow ratio in revascularization guidance
Authors: Oikonomou D , Gkini K P , Terentes-Printzios D , Gardikioti V , Dima I , Solomou E , Xydis P , Laina A , Aznaouridis K , Tsioufis K , Vlachopoulos C
Published: October 2021

Background/Introduction

Functional coronary stenosis severity has been associated with less clinical adverse events compared with plain invasive coronary angiography in guiding revascularization. Quantitative flow ratio (QFR) has proven to be a reliable tool of functional assessment of coronary lesions.

Purpose

To investigate the level of agreement between plain coronary angiography and QFR in guiding the decision to treat a coronary lesion.

Methods

We retrospectively performed an offline QFR analysis in consecutive patients who underwent coronary angiography in a single center. Patients with referral for coronary artery bypass graft surgery were excluded. We aimed to measure QFR in all vessels of each patient. All vessels with calculated QFR were divided into four groups based on whether percutaneous coronary intervention (PCI) was performed and on the QFR result with a cut-off point <0.8 indicating revascularization: Group A (PCI+, QFR <0.8); group B (PCI−, QFR >0.8); group C (PCI+, QFR >0.8); group D (PCI−, QFR <0.8) (Figure 1).

Results

We identified 785 patients with available coronary angiography satisfying the technical requirements of QFR software. QFR measurement in at least one vessel was feasible in 546 patients (70%). Mean age was 65.6 (±10.9) and 80% of patients were male. Acute coronary syndrome was the indication for coronary angiography in 36% of the cohort. QFR was calculated in 1193 vessels (∼51% of total vessels). In particular, QFR analysis was feasible in 448 (57%) left anterior descending (LAD), 457 (58%) left circumflex (LCX), and 288 (37%) right coronary arteries (RCA) coronary arteries. The most common reason for inability to calculate QFR was the absence of appropriate projections (30% of the missing cases). A mismatch in treatment strategy between coronary angiography and QFR result was detected in 151 (12.7%) vessels. In 78 (6.6%) cases PCI was performed while QFR was measured above 0.8 (group C). In 73 (6.1%) cases PCI was not performed while QFR was measured below 0.8 (Group D) (Figure 1). Among mismatch cases LAD was more likely to fall within group D whereas RCA was more often related with group C.

Conclusion

Discordance between plain coronary angiography and quantitative flow ratio regarding the decision to perform or to defer PCI was found in a relatively high proportion among patients undergoing coronary angiography. Prognostic evidence is warranted to determine the clinical significance of the mismatch between the two methods.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Is colchicine safe for cardiovascular indications?
Authors: Imazio M , Andreis A , Piroli F , Casula M , Paneva E , Avondo S , De Ferrari G M
Published: October 2021

Background

Colchicine has an emerging role in the cardiovascular field (e.g. acute and chronic coronary syndromes, pericarditis, atrial fibrillation), although, concerns for side effects, especially gastrointestinal, may limit its prescription.

Aims

We aimed at evaluating reported side effects of colchicine for cardiovascular indications.

Methods

We performed a meta-analysis of published randomized controlled trials on colchicine for the treatment of cardiovascular diseases. Random-effects meta-analysis was used to assess the risk of adverse events and drug withdrawal. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity.

Results

Among 14 188 patients, 7136 patients received colchicine while the other 7052 received placebo. The occurrence of any adverse event with colchicine was reported in 15.3 vs. 13.9% patients [relative risk (RR) 1.26, 95% confidence interval (CI) 0.96–1.64, P=0.09, see figure]. Gastrointestinal events were reported in 16.1 vs. 12.2% (RR 2.16, 95% CI 1.50–3.12, P<0.001), while diarrhoea was reported in 12.5 vs. 8.1% (RR 2.77, 95% CI 1.55–4.94, P<0.001). The risk of gastrointestinal events increased with daily dose and shorter treatment duration. Myalgias were observed in 21 vs. 18% patients (RR 1.16, 95% CI 1.02–1.32, P=0.03). Other adverse events such as myotoxicity, hepatic adverse events, hematologic adverse events, cutaneous adverse events, infection or death were not increased by colchicine treatment. Colchicine discontinuation was reported in 4.8 vs. 3.4% patients (RR 1.54, 95% CI 1.20–1.99, P<0.001).

Conclusions

Colchicine is associated with increased risk of gastrointestinal events and myalgias, but not of other adverse events. The risk of gastrointestinal events may be avoided with lower dose (0.5 mg/daily) and is inversely related to treatment duration, possibly due to early drug discontinuation or drug tolerance.

Funding Acknowledgement

Type of funding sources: None.