The latest medical research on Heart Failure

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Insights Into Myocardial Oxygenation and Cardiovascular Magnetic Resonance Tissue Biomarkers in Heart Failure With Preserved Ejection Fraction.

Circulation. Heart failure

The pathophysiology of heart failure with preserved ejection fraction is not well understood, but evidence strongly suggests involvement of microvascular dysfunction. We studied the myocardial oxygenation reserve as a direct marker of coronary vascular function and its relation to myocardial deformation and tissue characteristics by cardiovascular magnetic resonance (CMR).

In a dual-center case-control study, patients with heart failure and preserved ejection fraction (>50%) and healthy controls older than 50 years underwent quantitative CMR for ventricular volumes and functional assessment with feature tracking, as well as tissue characterization (T1, T2, extracellular volume). Coronary vascular function was measured by oxygenation-sensitive (OS)-CMR of the myocardial oxygenation response to a vasoactive breathing maneuver.

Twenty-nine patients completed the CMR exam. Compared with cutoffs derived from 12 control subjects, circumferential peak strain was attenuated in 97% of patients. Native T1 was elevated in 93%, extracellular volume was elevated in 83%. Sixty-six percent of patients revealed either regional or global myocardial edema, defined by an increased myocardial T2. An attenuated global myocardial oxygenation reserve (<4.4%) was observed in 96% of the patients (1.7±3.9% versus 9.1±5.3% in controls, P<0.001). This was correlated with septal wall thickness (r=-0.54, P=0.003), edema (myocardial T2; β=-0.26% oxygenation-sensitive/ms [95% CI, -0.49 to -0.03], P=0.029), and reduced diastolic strain rate (β=1.50% oxygenation-sensitive/s-1 [95% CI, 0.06-2.90], P=0.042).

In patients with clinical heart failure with preserved ejection fraction, vascular dysfunction as measured by an attenuated myocardial oxygenation reserve is associated with myocardial edema, a thicker septum, and diastolic dysfunction. A quantitative comprehensive CMR exam including oxygenation-sensitive-CMR allows for comprehensive imaging-based phenotyping of heart failure with preserved ejection fraction.

Acute Heart Failure in the 2021 ESC Heart Failure Guidelines: a scientific statement from the Association for Acute CardioVascular Care (ACVC) of the European Society of Cardiology.

European Heart Journal

The current European Society of Cardiology (ESC) Heart Failure Guidelines are the most comprehensive ESC document covering heart failure to date; h...

Ratio of Mixed Venous Oxygen Saturation-to-Pulmonary Capillary Wedge Pressure: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

Circulation. Heart failure

Hemodynamic values from right heart catheterization aid diagnosis and clinical decision-making but may not predict outcomes. Mixed venous oxygen saturation percentage and pulmonary capillary wedge pressure relate to cardiac output and congestion, respectively. We theorized that a novel, simple ratio of these measurements could estimate cardiovascular prognosis.

We queried Veterans Affairs' databases for clinical, hemodynamic, and outcome data. Using the index right heart catheterization between 2010 and 2016, we calculated the ratio of mixed venous oxygen saturation-to-pulmonary capillary wedge pressure, termed ratio of saturation-to-wedge (RSW). The primary outcome was time to all-cause mortality; secondary outcome was 1-year urgent heart failure presentation. Patients were stratified into quartiles of RSW, Fick cardiac index (CI), thermodilution CI, and pulmonary capillary wedge pressure alone. Kaplan-Meier curves and Cox proportional hazards models related comparators with outcomes.

Of 12 019 patients meeting inclusion criteria, 9826 had values to calculate RSW (median 4.00, interquartile range, 2.67-6.05). Kaplan-Meier curves showed early, sustained separation by RSW strata. Cox modeling estimated that increasing RSW by 50% decreases mortality hazard by 19% (estimated hazard ratio, 0.81 [95% CI, 0.79-0.83], P<0.001) and secondary outcome hazard by 28% (hazard ratio, 0.72 [95% CI, 0.70-0.74], P<0.001). Among the 3793 patients with data for all comparators, Cox models showed RSW best associated with outcomes (by both C statistics and Bayes factors). Furthermore, pulmonary capillary wedge pressure was superior to thermodilution CI and Fick CI. Multivariable adjustment attenuated without eliminating the association of RSW with outcomes.

In a large national database, RSW was superior to conventional right heart catheterization indices at assessing risk of mortality and urgent heart failure presentation. This simple calculation with routine data may contribute to clinical decision-making in this population.

The effect of the GoodSAM volunteer first-responder app on survival to hospital discharge following out-of-hospital cardiac arrest.

European Heart Journal

Bystander cardiopulmonary resuscitation and defibrillation can double survival to hospital discharge in out-of-hospital cardiac arrest. Mobile phone applications, such as GoodSAM, alerting nearby volunteer first-responders about out-of-hospital cardiac arrest could potentially improve bystander cardiopulmonary resuscitation and defibrillation, leading to better patient outcomes. The aim of this study was to determine GoodSAM's effect on survival to hospital discharge following out-of-hospital cardiac arrest.

We collected data from the Out-of-Hospital Cardiac Arrest Outcomes Registry (University of Warwick, UK) submitted by the London Ambulance Service (1 April 2016 to 31 March 2017) and East Midlands Ambulance Service (1 January 2018 to 17 June 2018) and matched out-of-hospital cardiac arrests to GoodSAM alerts. We constructed logistic regression models to determine if there was an association between a GoodSAM first-responder accepting an alert and survival to hospital discharge, adjusting for location type, presenting rhythm, age, gender, ambulance service response time, cardiac arrest witnessed status, and bystander actions. Survival to hospital discharge was 9.6% (393/4196) in London and 7.2% (72/1001) in East Midlands. A GoodSAM first-responder accepted an alert for out-of-hospital cardiac arrest in 1.3% (53/4196) cases in London and 5.4% (51/1001) cases in East Midlands. When a responder accepted an alert, the adjusted odds ratio for survival to hospital discharge was 3.15 (95% CI: 1.19-8.36, P = 0.021) in London and 3.19 (95% CI: 1.17-8.73, P = 0.024) in East Midlands.

Alert acceptance was associated with improved survival in both ambulance services. Alert acceptance rates were low, and challenges remain to maximize the potential benefit of GoodSAM.

Adding stress biomarkers to high-sensitivity cardiac troponin for rapid non-ST-elevation myocardial infarction rule-out protocols.

European Heart Journal

This study tested the hypothesis that combining stress-induced biomarkers (copeptin or glucose) with high-sensitivity cardiac troponin (hs-cTn) increases diagnostic accuracy for non-ST-elevation myocardial infarction (NSTEMI) in patients presenting to the emergency department.

The ability to rule-out NSTEMI for combinations of baseline hs-cTnT or hs-cTnI with copeptin or glucose was compared with the European Society of Cardiology (ESC) hs-cTnT/I-only rule-out algorithms in two independent (one Norwegian and one international multicentre) diagnostic studies. Among 959 patients (median age 64 years, 60.5% male) with suspected NSTEMI in the Norwegian cohort, 13% had NSTEMI. Adding copeptin or glucose to hs-cTnT/I as a continuous variable did not improve discrimination as quantified by the area under the curve {e.g. hs-cTnT/copeptin 0.91 [95% confidence interval (CI) 0.89-0.93] vs. hs-cTnT alone 0.91 (95% CI 0.89-0.93); hs-cTnI/copeptin 0.85 (95% CI 0.82-0.87) vs. hs-cTnI alone 0.93 (95% CI 0.91-0.95)}, nor did adding copeptin <9 mmol/L or glucose <5.6 mmol/L increase the sensitivity of the rule-out provided by hs-cTnT <5 ng/L or hs-cTnI <4 ng/L in patients presenting more than 3 h after chest pain onset (target population in the ESC-0 h-algorithm). The combination decreased rule-out efficacy significantly (both P < 0.01). These findings were confirmed among 1272 patients (median age 62 years, 69.3% male) with suspected NSTEMI in the international validation cohort, of which 20.7% had NSTEMI. A trend towards increased sensitivity for the hs-cTnT/I/copeptin combinations (97-100% vs. 91-97% for the ESC-0 h-rule-out cut-offs) was observed in the Norwegian cohort.

Adding copeptin or glucose to hs-cTnT/I did not increase diagnostic performance when compared with current ESC guideline hs-cTnT/I-only 0 h-algorithms.

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) update 2022.

European Heart Journal

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myoc...

Prognostic relevance of magnesium alterations in patients with a myocardial infarction and left ventricular dysfunction: insights from the EPHESUS trial.

European Heart Journal

Magnesium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). The relation between serum magnesium and clinical outcomes is insufficiently elucidated in this population.

The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hypomagnesemia and hypermagnesemia were defined as a serum magnesium <0.66 and >1.10 mmol/L, respectively. Linear mixed models and time-dependent Cox regression analysis were used to determine the effect of eplerenone on magnesium changes and the prognostic importance of magnesium. The co-primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV hospitalization. A total of 5371 patients had a post-baseline magnesium measurement. At baseline, 231 (4.3%) patients had hypomagnesemia and 271 (5.0%) patients had hypermagnesemia. During a median follow-up of 16 months, 682 (13%) developed hypomagnesemia and 512 (9.5%) hypermagnesemia. Eplerenone treatment did not result in a different magnesium level during follow-up (P = 0.14). After covariate adjustment hypo- and hypermagnesemia were not associated with a higher risk of CV events. Magnesium levels did not modulate the effect of a high potassium (>5 mmol/L) or low potassium (<4 mmol/L) on the clinical outcome. Baseline magnesium levels did not influence the treatment effect of eplerenone (P-interaction > 0.1 for all primary and secondary endpoints).

In patients with MI complicated by LVSD or HF, magnesium alterations were not associated with clinical outcomes nor did they influence the effect of eplerenone. Serum magnesium did not modulate the effect of potassium changes on clinical outcome or the treatment effect of eplerenone.


Intermittent Occlusion of the Superior Vena Cava to Improve Hemodynamics in Patients With Acutely Decompensated Heart Failure: The VENUS-HF Early Feasibility Study.

Circulation. Heart failure

Reducing congestion remains a primary target of therapy for acutely decompensated heart failure. The VENUS-HF EFS (VENUS-Heart Failure Early Feasibility Study) is the first clinical trial testing intermittent occlusion of the superior vena cava with the preCARDIA system, a catheter mounted balloon and pump console, to improve decongestion in acutely decompensated heart failure.

In a multicenter, prospective, single-arm exploratory safety and feasibility trial, 30 patients with acutely decompensated heart failure were assigned to preCARDIA therapy for 12 or 24 hours. The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events through 30 days. Secondary end points included technical success defined as successful preCARDIA placement, treatment, and removal and reduction in right atrial and pulmonary capillary wedge pressure. Other efficacy measures included urine output and patient-reported symptoms.

Thirty patients were enrolled and assigned to receive the preCARDIA system. Freedom from device- or procedure-related major adverse events was observed in 100% (n=30/30) of patients. The system was successfully placed, activated and removed after 12 (n=6) or 24 hours (n=23) in 97% (n=29/30) of patients. Compared with baseline values, right atrial pressure decreased by 34% (17±4 versus 11±5 mm Hg, P<0.001) and pulmonary capillary wedge pressure decreased by 27% (31±8 versus 22±9 mm Hg, P<0.001). Compared with pretreatment values, urine output and net fluid balance increased by 130% and 156%, respectively, with up to 24 hours of treatment (P<0.01).

We report the first-in-human experience of intermittent superior vena cava occlusion using the preCARDIA system to reduce congestion in acutely decompensated heart failure. PreCARDIA treatment for up to 24 hours was well tolerated without device- or procedure-related serious or major adverse events and associated with reduced filling pressures and increased urine output. These results support future studies characterizing the clinical utility of the preCARDIA system.

URL:; Unique identifier: NCT03836079.

MiR-150 Attenuates Maladaptive Cardiac Remodeling Mediated by Long Noncoding RNA MIAT and Directly Represses Profibrotic Hoxa4.

Circulation. Heart failure

MicroRNA-150 (miR-150) plays a protective role in heart failure (HF). Long noncoding RNA, myocardial infarction-associated transcript (MIAT) regulates miR-150 function in vitro by direct interaction. Concurrent with miR-150 downregulation, MIAT is upregulated in failing hearts, and gain-of-function single-nucleotide polymorphisms in MIAT are associated with increased risk of myocardial infarction (MI) in humans. Despite the correlative relationship between MIAT and miR-150 in HF, their in vivo functional relationship has never been established, and molecular mechanisms by which these 2 noncoding RNAs regulate cardiac protection remain elusive.

We use MIAT KO (knockout), Hoxa4 (homeobox a4) KO, MIAT TG (transgenic), and miR-150 TG mice. We also develop DTG (double TG) mice overexpressing MIAT and miR-150. We then use a mouse model of MI followed by cardiac functional, structural, and mechanistic studies by echocardiography, immunohistochemistry, transcriptome profiling, Western blotting, and quantitative real-time reverse transcription-polymerase chain reaction. Moreover, we perform expression analyses in hearts from patients with HF. Lastly, we investigate cardiac fibroblast activation using primary adult human cardiac fibroblasts and in vitro assays to define the conserved MIAT/miR-150/HOXA4 axis.

Using novel mouse models, we demonstrate that genetic overexpression of MIAT worsens cardiac remodeling, while genetic deletion of MIAT protects hearts against MI. Importantly, miR-150 overexpression attenuates the detrimental post-MI effects caused by MIAT. Genome-wide transcriptomic analysis of MIAT null mouse hearts identifies Hoxa4 as a novel downstream target of the MIAT/miR-150 axis. Hoxa4 is upregulated in cardiac fibroblasts isolated from ischemic myocardium and subjected to hypoxia/reoxygenation. HOXA4 is also upregulated in patients with HF. Moreover, Hoxa4 deficiency in mice protects the heart from MI. Lastly, protective actions of cardiac fibroblast miR-150 are partially attributed to the direct and functional repression of profibrotic Hoxa4.

Our findings delineate a pivotal functional interaction among MIAT, miR-150, and Hoxa4 as a novel regulatory mechanism pertinent to ischemic HF.

Heart Failure Spending Function: An Investment Framework for Sequencing and Intensification of Guideline-Directed Medical Therapies.

Circulation. Heart failure

Heart failure with reduced ejection fraction is managed with increasing numbers of guideline-directed medical therapies (GDMT). Benefits tend to be...

End-of-life care in the cardiac intensive care unit: a contemporary view from the Critical Care Cardiology Trials Network (CCCTN) Registry.

European Heart Journal

Increases in life expectancy, comorbidities, and survival with complex cardiovascular conditions have changed the clinical profile of the patients in cardiac intensive care units (CICUs). In this environment, palliative care (PC) services are increasingly important. However, scarce information is available about the delivery of PC in CICUs.

The Critical Care Cardiology Trials Network (CCCTN) Registry is a network of tertiary care CICUs in North America. Between 2017 and 2020, up to 26 centres contributed an annual 2-month snapshot of all consecutive medical CICU admissions. We captured code status at admission and the decision for comfort measures only (CMO) before all deaths in the CICU. Of 13 422 patients, 10% died in the CICU and 2.6% were discharged to palliative hospice. Of patients who died in the CICU, 68% were CMO at death. In the CMO group, only 13% were do not resuscitate/do not intubate at admission. The median time from CICU admission to CMO decision was 3.4 days (25th-75th percentiles: 1.2-7.7) and ≥7 days in 27%. Time from CMO decision to death was <24 h in 88%, with a median of 3.8 h (25th-75th 1.0-10.3). Before a CMO decision, 78% received mechanical ventilation and 26% mechanical circulatory support. A PC provider team participated in the care of 41% of patients who died.

In a contemporary CICU registry, comfort measures preceded death in two-thirds of cases, frequently without PC involvement. The high utilization of advanced intensive care unit therapies and lengthy times to a CMO decision highlight a potential opportunity for early engagement of PC teams in CICU.

Ten-year trends in mortality and complications following catheter ablation of atrial fibrillation.

European Heart Journal

Recent US studies report rising rates of mortality and in-hospital complications following catheter ablation of atrial fibrillation (AF) but whether this is a global phenomenon is uncertain.

To examine trends in 30-day mortality and complications following AF ablation in Australia and New Zealand (ANZ) from 2008-2017.

We identified 37,243 AF (mean age 62.4±11.5y, 29.6% females, 94.5% elective procedures) ablations using national hospitalisation data. The primary outcome was occurrence of any complication, including all-cause mortality, within 30 days of discharge. Trends were evaluated using logistic regression adjusting for changes in patient characteristics. Annual number of ablations increased from 1,359 (2008) to 5,115 (2017). Patients' age and rates of heart failure (9.8% to 10.6%), diabetes (6.8% to 12.4%), and chronic kidney disease (2.2% to 4.1%) also increased over time. From 2008-17, the overall rate of complications declined from 7.51% to 5.04% (adjusted odds ratio [aOR] 0.96[95%CI 0.94-0.97]/year). Rates of pericardial effusion (1.69% to 0.70%, aOR 0.93[0.89-0.97]), bleeding (4.49% to 2.74%, aOR 0.94[0.92-0.96]), and vascular injury (0.52% to 0.16%, aOR 0.91[0.85-0.98]), declined but rates of acute kidney injury (AKI) (0.15% to 0.68%, aOR 1.16[1.08-1.25]) and infection (0.15% to 0.57%, aOR 1.07[1.01-1.14]) increased over time. The overall 30-day mortality rate was low (0.11%) and unchanged (0.00% to 0.16%, aOR 0.99[0.88-1.11]).

Despite a five-fold increase in AF ablations and rising risk profile of patients, complications following AF ablation declined by 30% from 2008-2017 in ANZ. Procedure related death was uncommon and occurred in less than 1 in 850 patients.