Improving access to transcatheter aortic valve implantation across Europe by restructuring cardiovascular services: An expert council consensus statement.

Transcatheter aortic valve implantation (TAVI) is recommended for a growing range of patients with severe aortic stenosis in the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) 2021 Guidelines update. However, guideline implementation programs are needed to ensure the application of clinical recommendations which will favorably influence disease outcomes. An Expert Council was convened to identify whether cardiology services across Europe are set up to address the growing needs of patients with severe aortic stenosis for increased access to TAVI by identifying the key challenges faced in growing TAVI programs and mapping associated solutions. Wide variation exists across Europe in terms of TAVI availability and capacity to deliver the increased demand for TAVI in different countries. The recommendations of this Expert Council focus on the short-to-medium-term aspects where the most immediate, actionable impact can be achieved. The focus on improving procedural efficiency and optimizing the patient pathway via clinical practice and patient management demonstrates how to mitigate the current major issues of shortfall in catheterization laboratory, workforce, and bed capacity. Procedural efficiencies may be achieved through steps including streamlined patient assessment, the benchmarking of standards for minimalist procedures, standardized approaches around patient monitoring and conduction issues, and the implementation of nurse specialists and dedicated TAVI coordinators to manage organization, logistics, and early mobilization. Increased collaboration with wider stakeholders within institutions will support successful TAVI uptake and improve patient and economic outcomes. Further, increased education, collaboration, and partnership between cardiology centers will facilitate sharing of expertise and best clinical practice.

Long-Term Trajectories of Biomarkers, Functional, and Echocardiographic Parameters in Patients with Chronic Heart Failure from Dilated or Ischaemic Cardiomyopathy.

INTRODUCTION: The long-term evolution of clinical, echocardiographic, and laboratory parameters of cardiac function in patients with chronic heart failure (HF) with either reduced (HFrEF) or mildly reduced (HFmrEF) left ventricular ejection fraction (LVEF) is incompletely characterised. METHODS: We identified patients with chronic stable HF who presented at least twice to a university HF outpatient clinic between 1995 and 2021. Trajectories of NYHA functional class, LVEF, left ventricular internal end-diastolic diameter (LVIDD), NT-proBNP concentrations, and HF treatment over 10 years of follow-up were analysed using fractional polynomials. Analyses were repeated after stratifying patients according to aetiology (ischaemic vs. dilated) or HF category (HFrEF vs. HFmrEF). RESULTS: A total of 2,132 patients were included, of whom 51% had ischaemic and 49% had dilated HF. Eighty six percent and 14% were classified as HFrEF and HFmrEF, respectively. Mean LVEF was 28 ± 10%, and median NT-proBNP and estimated glomerular filtration rate values were 1,170 (385-3,176) pmol/L and 81 (62-100) mL/min/1.73 m2, respectively. Median follow-up was 5.2 (2.6-9.2) years. Overall, NYHA functional class and LVIDD trajectories were U-shaped, whereas LVEF and NT-proBNP concentrations markedly improved during the first year and remained stable thereafter. However, the evolution of HF parameters significantly differed with respect to HF category and aetiology, with greater improvements seen in patients with HFrEF of non-ischaemic origin. Improvements in HF variables were associated with optimization of HF therapy, notably with initiation and up-titration of renin-angiotensin-system blockers. CONCLUSION: This study provides insights into the natural history of HF in a large cohort of well-treated chronic HF outpatients with respect to subgroups of HF and different aetiologists.

Prognostic relevance of gradual weight changes on long-term mortality in chronic heart failure.

BACKGROUND AND AIMS: While obesity has been linked to better ouctomes (the obesity paradox), cachexia is associated with higher mortality in patients with heart failure with reduced ejection fraction (HFrEF). As opposed to overt cachexia, little is known about the prognostic impact of gradual, long-term weight changes in stable HFrEF. METHODS AND RESULTS: We included ambulatory patients with clinically stable chronic HFrEF on individually optimized treatment. Next to other clinical and functional parameters, changes in body weight over the past one (n = 733, group 1) or two (n = 636, group 2) years were recorded. Four-year mortality was analysed with respect to baseline BMI and changes in body weight or BMI using fractional polynomials. In addition, outcome was stratified by BMI categories (18.5-25 kg/m2: normal weight, >25-30 kg/m2: overweight, >30 kg/m2: obesity). An obesity paradox was present in both groups, with overweight and obese patients having the best prognosis. In both groups, a gradual weight gain of 5% was associated with the lowest mortality, whereas mortality steadily increases with increasing weight loss. Excessive weight gain >10% was also related to higher mortality. Stratification by baseline BMI categories revealed that weight loss was most detrimental in normal weight patients, whereas the prognostic impact of weight change was weaker in obese patients. CONCLUSION: In patients with chronic HFrEF, gradual weight loss is associated with steadily increasing mortality, whereas a weight gain of 5% is related to the best prognosis. Prevention of any inappropriate weight loss might be a therapeutic goal in HFrEF patient care.

The Obesity Paradox in Heart Failure: Is It Still Valid in Light of New Therapies?

BACKGROUND: Obesity increases the risk of cardiovascular disease and heart failure (HF). However, in patients with established HF, many studies observed greater survival with increasing adiposity. This counterintuitive observation has been termed the "obesity paradox." In recent years, new HF therapies have emerged that improve prognosis in patients with HF. Some of these, such as sodium-glucose cotransporter 2 inhibitors (SGLT2i), cause weight loss and may therefore interfere with the obesity paradox. SUMMARY: This article is a narrative review on the relationship between body weight and outcomes in patients with HF with special focus on new HF treatments. PubMed was searched for studies reporting the prognostic impact of obesity in HF from 2002 to February 22, 2022. More than 400 records were examined, with 150 being included in the present review. Literature provides evidence for an obesity paradox in a broad range of HF patients, including acute and chronic HF across the spectrum of left ventricular ejection fraction. It has been verified in HF patients treated with SGLT2i but not in those using sacubitril/valsartan. Cardiorespiratory fitness and the severity of HF seem to be important confounders of the obesity paradox in HF. While unintentional weight loss is associated with a poor prognosis in HF, weight loss associated with SGLT2i treatment appears safe. KEY MESSAGES: Consensus has yet to emerge as to whether the obesity paradox is a true phenomenon in HF. As cardiorespiratory fitness is strongly associated with prognosis and significantly modifies the relationship between adiposity and survival in HF, regular physical activity is recommended irrespective of the body weight. In HF patients with severe obesity, a modest weight reduction of 5-10% may be reasonable to improve HF symptoms and quality of life.

Comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for cardiovascular outcomes in type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2D). The comparative efficacy of individual SGLT2i remains unclear. We searched PubMed, www.clinicaltrials.gov and the Cochrane Central Register of Controlled Trials for randomised controlled trials exploring the use of canagliflozin, dapagliflozin, empagliflozin or ertugliflozin in patients with T2D. Comparators included placebo or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality and worsening heart failure (HF). Evidence was synthesised using network meta-analysis (NMA). Sixty-four trials reporting on 74,874 patients were included. The overall quality of evidence was high. When compared with placebo, empagliflozin and canagliflozin improved all three endpoints, whereas dapagliflozin improved worsening HF. When compared with other SGLT2i, empagliflozin was superior for all-cause and cardiovascular mortality reduction. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Ertugliflozin had no effect on any of the three endpoints investigated. Sensitivity analyses including extension periods of trials or excluding studies with a treatment duration of < 52 weeks confirmed the main results. Similar results were obtained when restricting mortality analyses to patients included in cardiovascular outcome trials (n = 38,719). Empagliflozin and canagliflozin improved survival with empagliflozin being superior to the other SGLT2i. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Prospective head-to-head comparisons would be needed to confirm these results.

Relative Efficacy of Spironolactone, Eplerenone, and cAnRenone in patients with Chronic Heart failure (RESEARCH): a systematic review and network meta-analysis of randomized controlled trials.

This study aims to assess the comparative benefit and risk profile of treatment with mineralocorticoid receptor antagonists (MRAs) with regard to all-cause mortality (primary endpoint), cardiovascular mortality, or heart failure (HF)-related hospitalization (secondary endpoints) and the safety endpoints hyperkalemia, acute renal failure, and gynecomastia in patients with chronic HF. We conducted a systematic review and network meta-analysis following PRISMA-P and PRISMA-NMA guidelines. From 16 different sources, 14 randomized controlled trials totaling 12,213 patients testing an active treatment of either spironolactone, eplerenone, or canrenone/potassium-canreonate in adults with symptomatic HF due to systolic dysfunction reporting any of the above endpoints were retained. Efficacy in comparison to placebo/standard medical care with respect to all-cause mortality was confirmed for spironolactone and eplerenone while no conclusion could be drawn for canrenone (HR 0.69 (0.62; 0.77), 0.82 (0.75; 0.91), and 0.50 (0.17; 1.45), respectively). Indirect comparisons hint a potential (non-significant) preference of spironolactone over eplerenone (HR 0.84 (0.68; 1.03)). The overall risk of bias was low to intermediate. Results for secondary endpoints as well as sensitivity analyses essentially mirrored these findings. The beta-blocker adjusted meta-analysis for the primary endpoint showed the same tendency as the unadjusted one (HR 0.39 (0.07; 2.03)). Results need to be interpreted with caution, though, as the resultant mix of patient- and study-level covariates produced unstable statistical modeling. We found no significant and systematic superiority of either MRA regarding efficacy toward all endpoints considered in both direct and indirect comparisons.

Cross-lagged analyses of the bidirectional relationship between depression and markers of chronic heart failure.

BACKGROUND: Depression is common in patients with chronic heart failure (CHF) and is a predictor of rehospitalization and mortality. However, the complex bidirectional relationships between these two conditions are barely understood. We investigated the course of depression and markers of CHF (New York Heart Association [NYHA] functional class, N-terminal-prohormone B-type natriuretic peptide [NT-proBNP], and left ventricular ejection fraction [LVEF]) in a longitudinal study over a period of 2 years, using three assessment points. METHODS: Data of n = 446 patients with documented CHF were analyzed using structural equation modeling. Specifically, a Bayesian cross-lagged structural equation model was applied. RESULTS: Our study revealed that an aggravation of depression predicted an increase in NYHA functional class (significant cross-lagged effect γh = 0.103, 95% confidence interval [CI] [0.017; 0.194]), whereas an increase in NYHA functional class did not predict an aggravation of depression (γd = 0.002 95% CI [-0.057; 0.194]). This association was found only for NYHA functional class and depression-not for NT-proBNP and LVEF. CONCLUSIONS: Experiencing depression and associated symptoms, such as lack of energy and fatigue, may lead to a further decrease of functional capacity, and consequently to a higher NYHA functional class in CHF patients. As NYHA functional class is associated with higher mortality, this may be a critical development for affected patients. Further studies are required to investigate whether or not this association could be an essential key that explains the pathway from depression to increased mortality in heart failure patients.

Benefits of peritoneal ultrafiltration in HFpEF and HFrEF patients.

BACKGROUND: Peritoneal ultrafiltration (pUF) in refractory heart failure (HF) reduces the incidence of decompensation episodes, which is of particular significance as each episode incrementally adds to mortality. Nevertheless, there are insufficient data about which patient cohort benefits the most. The objective of this study was to compare pUF in HFrEF and HFpEF, focusing on functional status, hospitalizations, surrogate endpoints and mortality. METHODS: This study involves 143 patients, who could be classified as either HFpEF (n = 37, 25.9%) or HFrEF (n = 106, 74.1%) and who received pUF due to refractory HF. RESULTS: Baseline eGFR was similar in HFrEF (23.1 ± 10.6 mg/dl) and HFpEF (27.8 ± 13.2 mg/dl). Significant improvements in NYHA class were found in HFpEF (3.19 ± 0.61 to 2.72 ± 0.58, P <  0.001) and HFrEF (3.45 ± 0.52 to 2.71 ± 0.72, P <  0.001). CRP decreased in HFrEF (19.4 ± 17.6 mg/l to 13.7 ± 21.4 mg/l, P = 0.018) and HFpEF (33.7 ± 52.6 mg/l to 17.1 ± 26.3 mg/l, P = 0.004). Body weight was significantly reduced in HFrEF (81.1 ± 14.6 kg to 77.2 ± 15.6 kg, P = 0.003) and HFpEF (86.9 ± 15.8 kg to 83.1 ± 15.9 kg, P = 0.005). LVEF improved only in HFrEF (25.9 ± 6.82% to 30.4 ± 12.2%, P = 0.046). BCR decreased significantly in HFrEF and HFpEF (55.7 ± 21.9 to 34.3 ± 17.9 P > 0.001 and 50.5 ± 68.9 to 37.6 ± 21.9, P = 0.006). Number of hospitalization episodes as well as number of hospitalization days decreased significantly only in HFpEF (total number 2.88 ± 1.62 to 1.25 ± 1.45, P <  0.001, days 40.4 ± 31.7 to 18.3 ± 22.5 days, P = 0.005). CONCLUSIONS: pUF offers various benefits in HFpEF and HFrEF, but there are also substantial differences. In particular, hospitalization rates were found to be significantly reduced in HFpEF patients, indicating a greater medical and economical advantage. However, LVEF was only found to be improved in HFrEF patients. While pUF can now be regarded as an option to supplement classical HF therapy, further studies are desirable to obtain specifications about pUF in HFpEF, HFmEF and HFrEF patients.

READY: relative efficacy of loop diuretics in patients with chronic systolic heart failure-a systematic review and network meta-analysis of randomised trials.

The majority of patients with chronic heart failure (HF) receive long-term treatment with loop diuretics. The comparative effectiveness of different loop diuretics is unknown. We searched PubMed, clinicaltrials.gov , the Cochrane Central Register of Controlled Trials and the European Union Clinical Trials Register for randomised clinical trials exploring the efficacy of the loop diuretics azosemide, bumetanide, furosemide or torasemide in patients with HF. Comparators included placebo, standard medical care or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, HF-related hospitalisation and any combined endpoint thereof. Hypokalaemia and acute renal failure were defined as additional safety endpoints. Evidence was synthesised using network meta-analysis (NMA). Thirty-four trials reporting on 2647 patients were included. The overall quality of evidence was rated as moderate. NMA demonstrated no significant differences between loop diuretics with respect to all-cause mortality, cardiovascular mortality or hypokalaemia. In contrast, torasemide ranked best in terms of HF hospitalisation, and there was a trend towards benefits with torasemide with regard to occurrence of acute renal failure. Sensitivity analyses excluding trials with a follow-up < 6 months, trials with a cross-over design and those including < 25 patients confirmed the main results. We found no significant superiority of either loop diuretic with respect to mortality and safety endpoints. However, clinicians may prefer torasemide, as it was associated with fewer HF-related hospitalisations.

Effect of Availability of Transcatheter Aortic-Valve Replacement on Clinical Practice.

BACKGROUND: Since the adoption of transcatheter aortic-valve replacement (TAVR), questions have been raised about its effect on clinical practice in comparison with the effect of surgical aortic-valve replacement, which is considered the current standard of care. Complete nationwide data are useful in examining how the introduction of a new technique influences previous clinical standards. METHODS: We analyzed data on characteristics of patients and in-hospital outcomes for all isolated TAVR and surgical aortic-valve replacement procedures performed in Germany from 2007 to 2013. RESULTS: In total, 32,581 TAVR and 55,992 surgical aortic-valve replacement procedures were performed. The number of TAVR procedures increased from 144 in 2007 to 9147 in 2013, whereas the number of surgical aortic-valve replacement procedures decreased slightly, from 8622 to 7048. Patients undergoing TAVR were older than those undergoing surgical aortic-valve replacement (mean [±SD] age, 81.0±6.1 years vs. 70.2±10.0 years) and at higher preoperative risk (estimated logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 22.4% vs. 6.3%, on a scale of 0 to 100%, with higher scores indicating greater risk and a score of more than 20% indicating high surgical risk). In-hospital mortality decreased in both groups between 2007 and 2013 (from 13.2% to 5.4% with TAVR and from 3.8% to 2.2% with surgical aortic-valve replacement). The incidences of stroke, bleeding, and pacemaker implantation (but not acute kidney injury) also declined. CONCLUSIONS: The use of TAVR increased markedly in Germany between 2007 and 2013; the concomitant reduction in the use of surgical aortic-valve replacement was moderate. Patients undergoing TAVR were older and at higher procedural risk than those undergoing surgical aortic-valve replacement. In-hospital mortality decreased in both groups but to a greater extent among patients undergoing TAVR. (Funded by the Heart Center, Freiburg University.).

Percutaneous repair of mitral valve regurgitation in patients with severe heart failure: comparison with optimal medical treatment.

BACKGROUND: Occurrence of severe mitral valve (MV) regurgitation (MR) is an independent negative predictor of mortality in patients with severe systolic heart failure (HF). This study examines clinical effects and cardiac reverse remodelling in patients with severe systolic HF receiving percutaneous mitral valve repair (PMVR) using MitraClip in comparison to patients receiving optimal medical therapy only. METHODS: Between 2010 and 2014, 86 patients (Society of Thoracic Surgeons score: 10.5% ± 1.2%) with severe HF (left ventricular [LV] ejection fraction; LVEF: 25% ± 2%; LV endsystolic diameter [LVESD]: 55 ± 3 mm) and severe MR received PMVR using MitraClip. Cardiac reverse remodelling and clinical parameters were compared to HF patients with severe MR (from our HF outpatient clinic; n = 69; LVEF: 26% ± 1.4%; LVESD: 53 ± 2 mm) receiving optimal medical therapy (OMT) only. All patients received stable OMT and were characterised by echocardiography, 6-minwalk-distance test and cardiac biomarkers within a 24 months observation period. RESULTS: PMVR in patients with end-stage HF and severe MR resulted in reduction of MR and significant additional cardiac reverse remodelling (LVEF: 26 ± 1.4 vs. 33% ± 2%, p < .05; LVESD: 53 ± 2 vs. 47 ± 2 mm, p < .05) over the 24 months observation period as compared to pharmacologically-only managed comparators. CONCLUSIONS: Both OMT and PMVR cause cardiac reverse remodelling and relief of symptoms in patients with HF and severe MR. PMVR results in significant additional cardiac reverse remodelling compared to pharmacologically-only managed patients.

Hemodynamic Determinants of the Biologic Variation of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Stable Systolic Chronic Heart Failure.

BACKGROUND CONTEXT: Biologic variation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) may affect blood levels and risk stratification. The sources of NT-proBNP variation are unknown. METHODS AND RESULTS: We performed NT-proBNP measurements and clinical and hemodynamic assessments in 50 patients with heart failure with reduced ejection fraction (HFrEF) who met criteria for clinical stability over 2 time intervals. Hemodynamic variables were measured with the use of inert gas rebreathing and impedance cardiography. Heart rhythm was monitored with the use of external electrocardiographic event recorders throughout the study. Determinants of NT-proBNP-levels and both absolute (ΔNT-proBNPabs) and relative (ΔNT-proBNP%) changes at 1-week and 2-week intervals were identified with the use of univariable and multivariable linear mixed-effects models and linear regression analyses, respectively. Clinical and hemodynamic variables did not significantly change between study visits. The individual variation of NT-proBNP at 2 weeks was 9.2% (range 3.9%-18.6%). Weight and glomerular filtration rate were independently associated with baseline NT-proBNP concentrations (P = .01 and P = .005, respectively). There was no relationship between absolute and relative changes of NT-proBNP at 1-week intervals and changes in clinical and hemodynamic variables. Absolute change of NT-proBNP at 2-week intervals was associated with absolute change in left cardiac work index (P = .008), and relative change in NT-proBNP at 2-week intervals was determined by relative change of thoracic fluid content index (P = .008) and diastolic blood pressure (P = .01). The coefficients of determination (R2) for the multivariable models with Δ1wkNT-proBNPabs, Δ2-weeksNT-proBNPabs, Δ1wkNT-proBNP%, and Δ2wksNT-proBNP% as dependent variables were 0.21, 0.19, 0.10, and 0.32, respectively. CONCLUSIONS: In patients with stable HFrEF, changes in clinical and hemodynamic variables only marginally contribute to the variation of NT-proBNP.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). METHODS: In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. RESULTS: ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. CONCLUSIONS: In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored.

Left ventricular long axis strain: a new prognosticator in non-ischemic dilated cardiomyopathy?

BACKGROUND: Long axis strain (LAS) has been shown to be a fast assessable parameter representing global left ventricular (LV) longitudinal function in cardiovascular magnetic resonance (CMR). However, the prognostic value of LAS in cardiomyopathies with reduced left ventricular ejection fraction (LVEF) has not been evaluated yet. METHODS AND RESULTS: In 146 subjects with non-ischemic dilated cardiomyopathy (NIDCM, LVEF ≤45 %) LAS was assessed retrospectively from standard non-contrast SSFP cine sequences by measuring the distance between the epicardial border of the left ventricular apex and the midpoint of a line connecting the origins of the mitral valve leaflets in end-systole and end-diastole. The final values were calculated according to the strain formula. The primary endpoint of the study was defined as a combination of cardiac death, heart transplantation or aborted sudden cardiac death and occurred in 24 subjects during follow-up. Patients with LAS values > -5 % showed a significant higher rate of cardiac events independent of the presence of late gadolinium enhancement (LGE). The multivariate Cox regression analysis revealed that LVEDV/BSA (HR: 1.01, p < 0.05), presence of LGE (HR: 2.51, p < 0.05) and LAS (HR: 1.28, p < 0.05) were independent predictors for cardiac events. In a sequential cox regression analysis LAS offered significant incremental information (p < 0.05) for the prediction of outcome in addition to LGE and LVEDV/BSA. Using a dichotomous three point scoring model for risk stratification, including LVEF <35 %, LAS > -10 % and the presence of LGE, patients with 3 points had a significantly higher risk for cardiac events than those with 2 or less points. CONCLUSION: Assessment of long axis function with LAS offers significant incremental information for the prediction of cardiac events in NIDCM and improves risk stratification beyond established CMR parameters.

Biomarker changes after strenuous exercise can mimic pulmonary embolism and cardiac injury--a metaanalysis of 45 studies.

BACKGROUND: Biomarkers are well established for diagnosis of myocardial infarction [cardiac troponins, high-sensitivity cardiac troponins (hs-cTn)], exclusion of acute and chronic heart failure [B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP)] and venous thromboembolism (d-dimers). Several studies have demonstrated acute increases in cardiac biomarkers and altered cardiac function after strenuous sports that can pretend a cardiovascular emergency and interfere with state-of-the-art clinical assessment. METHODS: We performed a systematic review and metaanalysis of biomarker and cardiovascular imaging changes after endurance exercise. We searched for observational studies published in the English language from 1997 to 2014 that assessed these biomarkers or cardiac function and morphology directly after endurance exercise. Of 1787 identified abstracts, 45 studies were included. RESULTS: Across all studies cardiac troponin T (cTnT) exceeded the cutoff value (0.01 ng/mL) in 51% (95% CI, 37%-64%) of participants. The measured pooled changes from baseline for high-sensitivity cTnT (hs-cTnT) were +26 ng/L (95% CI, 5.2-46.0), for cTnI +40 ng/L (95% CI, 21.4; 58.0), for BNP +10 ng/L (95% CI, 4.3; 16.6), for NT-proBNP +67 ng/L (95% CI, 49.9; 84.7), and for d-dimer +262 ng/mL (95% CI, 165.9; 358.7). Right ventricular end diastolic diameter increased and right ventricular ejection fraction as well as the ratio of the early to late transmitral flow velocities decreased after exercise, while no significant changes were observed in left ventricular ejection fraction. CONCLUSIONS: Current cardiovascular biomarkers (cTnT, hs-cTnT, BNP, NT-proBNP, and d-dimer) that are used in clinical diagnosis of pulmonary embolism, acute coronary syndrome, and heart failure are prone to alterations due to strenuous exercise. Hence, it is necessary to take previous physical exercise into account when a cardiac emergency is suspected.

Potentially modifiable correlates of functional status in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) patients suffer from multiple and agonizing symptoms like shortness of breath and reduced functional status, the latter of which is usually assessed using New York Heart Association (NYHA) functional class. PURPOSE: In order to identify potentially modifiable factors of reduced functional status in patients with CHF, we investigated somatic and psychosocial correlates of NYHA functional class. We subsequently compared the results to correlates of left ventricular ejection fraction (LVEF) as an objective parameter of disease severity. METHODS: The cross-sectional study (n = 314) was part of the German Heart Failure Network. Data were analysed using a logistic regression modelling process. RESULTS: In the final regression model, NYHA functional class was only significantly associated with depression (odds ratio (OR) = 1.18; 95% confidence interval (CI) = 1.09-1.27) and multimorbidity (OR = 1.17; 95% CI = 1.04-1.32). LVEF was associated with amino-terminal pro-brain natriuretic peptide (NT-proBNP) (OR = 0.60; 95% CI = 0.44-0.82), aetiology of CHF (OR = 2.08; 95% CI = 1.11-3.90), and smoking (OR = 2.21; 95% CI = 1.25-3.91). CONCLUSIONS: Whereas LVEF was not related to depression, our data revealed a close association between functional status (as assessed by NYHA functional class) and depression in patients with CHF, even after adjusting for cardiac and socio-demographic variables. Different forms of underlying causal mechanisms could be suspected; it appears promising to further investigate this specific interaction. In any event, pending further investigation, our results underscore the need to examine CHF patients with respect to both somatic symptom burden and potential depressive disorders.

Somatic symptom profile in patients with chronic heart failure with and without depressive comorbidity.

Background: Patients with chronic heart failure (CHF) frequently suffer from depressive comorbidity. CHF and depressive comorbidity can cause somatic symptoms. The correct attribution of somatic symptoms is important. Thus, we aimed to assess potential differences in somatic symptom severity between CHF patients with and without depressive comorbidity. Methods: We evaluated depressive comorbidity using the Patient Health Questionnaire-9 (PHQ-9), somatic symptom severity with the Patient Health Questionnaire-15 (PHQ-15), and sociodemographic and medical variables in 308 CHF outpatients. To compare somatic symptom severity between CHF patients with and without depressive comorbidity, we conducted item-level analyses of covariance. Results: Of the 308 participating patients, 93 (30.3%) met the PHQ-9 criteria for depressive comorbidity. These patients did not differ from those without depressive comorbidity with regard to age, sex, left ventricular function, and multimorbidity. Patients with depressive comorbidity scored significantly higher on ten out of thirteen PHQ-15 items than patients without depressive comorbidity. The largest effect sizes (0.71-0.80) were shown for symptoms of headache, chest pain, shortness of breath, and palpitations, and the latter three were potentially attributable to heart failure. Conclusions: Among patients with CHF, somatic symptoms are more pronounced in those with depressive comorbidity than those without depressive comorbidity. This finding is especially true for cardiac symptoms independent of CHF severity. The potential interpretation of somatic symptoms as correlates of depressive comorbidity must be recognized in clinical practice.

Influence of prior myocardial infarction on outcome in patients with ischaemic HFrEF: insights from the EVIdence based TreAtment in Heart Failure (EVITA-HF) registry.

BACKGROUND: There is scarce information about the influence of prior myocardial infarction (pMI) on outcomes in patients (pts) with ischaemic HFrEF. We analysed data from the EVIdence based TreAtment in Heart Failure (EVITA-HF) registry. METHODS: EVITA-HF comprises web-based case report data on demography, diagnostic measures, adverse events and 1-year follow-up of patients hospitalized for chronic heart failure ≥ 3 months (CHF) and an ejection fraction ≤ 40%. In the present study, we focused on the outcomes of pts with and without pMI in ischaemic HFrEF. RESULTS: Between February 2009 and November 2015, a total of 2075 consecutive pts with ischaemic HFrEF were included from 16 centres in Germany. A total of 81.2% were male, and the mean age was 71 years. A total of 61.5% of the pts with ischaemic HFrEF had a history of pMI. These pts were treated less often with PCI (20.0 vs. 31.0%, p < 0.001) or CABG (3.8 vs. 7.7%, p < 0.001). They more often received an ICD (40.9 vs. 28.7%, p < 0.001), but less often a CRT-D (11.3 vs. 19.4%, p < 0.001). After multivariate adjustment, pts with pMI had a greater all-cause mortality after 1 year than those without pMI (hazard ratio 1.4; 95% CI, 1.10-1.79, p = 0.007). The combined endpoint of death, resuscitation or ICD shock after 1 year was greater in patients with pMI (20.8 vs. 16.4%, p = 0.03). Mobility was more often reduced in pts with pMI (46.8% vs. 40.1%, p = 0.03), and overall health status was more frequently worse in patients with pMI than in those 12 months ago (23.1 vs. 15.9%, p = 0.01). More than a quarter of the pts with ischaemic HFrEF were anxious or depressive. CONCLUSION: pMI in patients with CHF and ischaemic HFrEF was associated with increased mortality, increased event rates, and worsened health status. Hence, the subgroup of pts with ischaemic HFrEF and pMI is at higher risk and deserves special attention.

Cost-Effectiveness of SAPIEN 3 Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in German Severe Aortic Stenosis Patients at Low Surgical Mortality Risk.

INTRODUCTION: In the randomized PARTNER 3 trial, transcatheter aortic valve implantation (TAVI) with the SAPIEN 3 device significantly reduced a composite of all-cause death, stroke, and rehospitalization, compared with surgical aortic valve replacement (SAVR), in patients with severe symptomatic aortic stenosis and low risk of surgical mortality. Furthermore, TAVI has been shown to be cost-effective in low-risk patients, compared with SAVR, in a number of countries. This study aimed to determine the cost-effectiveness of TAVI with SAPIEN 3 versus SAVR in Germany. METHODS: A previously published two-stage Markov-based model that captured clinical outcomes from the PARTNER 3 trial was adapted for the German context using the German Statutory Health Insurance perspective. The model had a lifetime horizon. The cost-utility analysis estimated changes in direct healthcare costs as well as survival and health-related quality of life using TAVI with SAPIEN 3 compared with SAVR. RESULTS: TAVI with SAPIEN 3 increased quality-adjusted life years (QALYs) by + 0.72 at an increased cost of €8664 per patient. The incremental cost-effectiveness/QALY ratio was €12,037, which fell below that of other cardiovascular interventions in use in Germany. The cost-effectiveness of TAVI over SAVR remained robust across multiple challenging scenarios and was driven by lower longer-term management costs compared with SAVR. CONCLUSIONS: TAVI with SAPIEN 3 appears to be a clinically meaningful, cost-effective treatment option over SAVR for patients with severe symptomatic aortic stenosis and low risk for surgical mortality in Germany. CLINICAL TRIAL REGISTRATION NUMBER: www. CLINICALTRIALS: gov identifier: NCT02675114.

Aspirin use and bleeding events during thrombocytopenia after autologous stem-cell transplantation for multiple myeloma.

Background: In patients with cardiovascular (CV) comorbidities that necessitate antiplatelet therapy (APT), its optimal management during chemotherapy-induced thrombocytopenia remains elusive, as the risk of bleeding has to be balanced against the risk of CV events. The purpose of this study was to assess the risk for bleeding with APT during thrombocytopenia in patients with multiple myeloma undergoing high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT) with and without acetylsalicylic acid (ASA) as comedication. Methods: We assessed patients who underwent ASCT at the Heidelberg University Hospital between 2011 and 2020 for bleeding events, management strategies for ASA intake during thrombocytopenia, transfusion requirements, and the occurrence of CV events. Results: There were 57/1,113 patients who continued ASA until at least 1 day after ASCT; thus, a continuous platelet inhibition during thrombocytopenia was assumed. Most of the patients (41/57) continued ASA until they had a platelet count of 20-50/nl. This range reflects the kinetics of thrombocytopenia and nondaily measurements of platelets during ASCT. A tendency toward a higher risk for bleeding events in the ASA group was demonstrated (1.9% (control group) vs. 5.3% (ASA), p = 0.082). The risk factors for bleeding in multivariate analysis were the duration of thrombocytopenia < 50/nl, a history of gastrointestinal bleeding, and diarrhea. The factors predicting the duration of thrombocytopenia were age >60 years, a hematopoietic stem-cell transplantation comorbidity index ≥3, and an impaired bone marrow reserve at admission. CV events occurred in three patients; none of them took ASA or had an indication for APT. Conclusions: The intake of ASA until thrombocytopenia with a platelet count of 20-50/nl appears safe, although an elevated risk cannot be excluded. If ASA is indicated for the secondary prevention of CV events, the evaluation of risk factors for bleeding and a prolonged time of thrombocytopenia before conditioning is crucial to adapt the strategy for ASA intake during thrombocytopenia.