Twenty-one adult patients were randomised to receive ghrelin on days 1 and 8 and placebo on days 4 and 11 or vice versa, given intravenously over a 60-min period before lunch: 10 received 2 microg ...kg(-1) (lower-dose) ghrelin; 11 received 8 microg kg(-1) (upper-dose) ghrelin. Active and total ghrelin, growth hormone (GH), and insulin-like growth factor 1 levels were monitored at baseline (4-5 days before day 1), during treatment days, and at end of study (day 17/18). Drug-related adverse events (assessed by NCI-CTC-toxicity criteria and cardiac examination) did not differ between ghrelin and placebo. No grade 3/4 toxicity or stimulation of tumour growth was observed. The peak increase of GH, a biological marker of ghrelin action, was 25 ng ml(-1) with lower-dose and 42 ng ml(-1) with upper-dose ghrelin. Morning fasting total ghrelin levels were higher (P<0.05) for upper-dose patients at end of study (3580 pg ml(-1)) than at baseline (990 pg ml(-1)). Insulin-like growth factor 1 levels did not change. At day 8, 81% of patients preferred ghrelin to placebo as against 63% at the end of study. Nutritional intake and eating-related symptoms, measured to explore preliminary efficacy, did not differ between ghrelin and placebo. Ghrelin is well tolerated and safe in patients with advanced cancer. For safety, tolerance, and patients' preference for treatment, no difference was observed between the lower- and upper-dose group.
Background
Limited data are available on patients with chronic lung disease (CLD) presenting with acute myocardial infarction (AMI). We aimed to analyse baseline characteristics, treatment and ...outcome of those patients enrolled in the Swiss nationwide prospective AMIS Plus registry.
Methods
All AMI patients enrolled between January 2002 and December 2021 with data on CLD, as defined in the Charlson Comorbidity Index, were included. The primary endpoints were in‐hospital mortality and major adverse cardiac and cerebrovascular events (MACCE), defined as all‐cause death, reinfarction and cerebrovascular events. Baseline characteristics, in‐hospital treatments and outcomes were analysed using descriptive statistics and logistic regression.
Results
Among 53,680 AMI patients enrolled during this time, 5.8% had CLD. Compared with patients without CLD, CLD patients presented more frequently with non‐ST‐elevation myocardial infarction (MI) and type 2 MI (12.8% vs. 6.5%, p < 0.001). With respect to treatment, CLD patients were less likely to receive P2Y12 inhibitors (p < 0.001) and less likely to undergo percutaneous coronary interventions (68.7% vs. 82.5%; p < 0.001). In‐hospital mortality declined in AMI patients with CLD over time (from 12% in 2002 to 7.3% in 2021). Multivariable regression analysis showed that CLD was an independent predictor for MACCE (adjusted OR was 1.28 95% CI 1.07–1.52, p = 0.006).
Conclusion
Patients with CLD and AMI were less likely to receive evidence‐based pharmacologic treatments, coronary revascularization and had a higher incidence of MACCE during their hospital stay compared to those without CLD. Over 20 years, in‐hospital mortality was significantly reduced in AMI patients, especially in those with CLD.
We analysed patients with acute myocardial infarction (AMI) and chronic lung disease (CLD) over 20 years. Primary endpoints of this study were in‐hospital and major cardiac and cerebrovascular events. Patients with CLD were less likely to receive percutaneous coronary interventions than those without CLD. Non‐ST‐elevation myocardial infarction (MI) and type 2 MI were more likely to occur in patients with CLD. In‐hospital mortality and MACCE declined in AMI patients, especially in those with CLD over time.
Aims
While the conditions of heart failure (HF) with reduced (HFrEF, LVEF < 40%) and preserved (HFpEF, LVEF ≥ 50%) left ventricular ejection fraction (LVEF) are well characterized, it is unknown ...whether patients with HF and mid‐range LVEF (HFmrEF, LVEF 40–49%) have to be regarded as a separate clinical entity. The aim of this study was to characterize these three populations and to compare outcome and response to therapy.
Methods and results
The analysis was based on the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME‐CHF) comprising a population with established HF including the whole spectrum of LVEF. Of the 622 patients, 108 (17%) were classified as having HFmrEF. This group was in general found to be ‘intermediate’ regarding clinical characteristics with a comparable and high burden of comorbidities and equally impaired quality of life but was more likely to have coronary artery disease as compared with the HFpEF group. During a median follow‐up of 794 days, mortality was 39.7% without significant differences between groups. N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP)‐guided as compared with standard therapy resulted in improved survival free of HF hospitalizations in HFrEF and HFmrEF, but not in HFpEF.
Conclusion
Although the ‘intermediate’ clinical profile of HFmrEF between HFrEF and HFpEF would support the conclusion that HFmrEF is a distinct clinical entity, we hypothesize that HFmrEF has to be categorized as HFrEF because of the high prevalence of coronary artery disease and the similar benefit of NT‐proBNP‐guided therapy in HFrEF and HFmrEF, in contrast to HFpEF.
Aims
The aim of this study was to evaluate whether biomarkers reflecting pathophysiological pathways are different between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) ...and whether the prognostic value of biomarkers is different in HFpEF vs. HFrEF.
Methods and results
A total of 458 HFrEF (LVEF ≤40%) and 112 HFpEF (LVEF ≥50%) patients aged ≥60 years with NYHA class ≥II from TIME‐CHF were included. Endpoints are 18‐month overall and HF hospitalization‐free survival. After correction for baseline characteristics that differed between the HF types, i.e. age, gender, body mass index, systolic blood pressure, cause of HF, and AF, HFpEF patients exhibited higher soluble interleukin 1 receptor‐like 1 ST2; 37.6 (28.5–54.7) vs. 35.7 (25.6–52.2), P = 0.02, high sensitivity C‐reactive protein (hsCRP; 8.54 (3.39–25.86) vs. 6.66 (2.42–15.39), P = 0.01), and cystatin‐C 1.94 (1.57–2.37) vs. 1.75 (1.39–2.12), P = 0.01. In contrast, HFrEF patients exhibited higher NT‐proBNP 2142 (1473–4294) vs. 4202 (2239–7411), P < 0.001, high sensitivity troponin T hsTnT; 27.7 (16.8–48.0) vs. 32.4 (19.2–59.0), P = 0.03, and haemoglobin 124 (110–135) vs. 134 (122–145), P < 0.001. In addition to these clinical characteristics, NT‐proBNP, haemoglobin, cystatin‐C, hsTnT, and ST2 improved the area under the curve from 0.86 (0.82–0.89) to 0.91 (0.87–0.94; P < 0.001) for discriminating HFpEF from HFrEF. There were no significant interactions between HFpEF and HFrEF when considering the prognostic value of the investigated biomarkers (P > 0.10 for both endpoints), except for cystatin‐C which had less prognostic impact in HFpEF (P < 0.01).
Conclusion
Biomarker levels suggest a different amount of activation of several pathophysiological pathways between HFpEF and HFrEF. No important differences in the prognostic value of biomarkers in HFpEF vs. HFrEF were found except for cystatin‐C, and for NT‐proBNP in the NT‐proBNP‐guided study arm only, both of which had less prognostic value in HFpEF.
Trial registration
ISRCTN43596477
Obstructive sleep apnea (OSA) is associated with cardiovascular risk factors, cardiovascular diseases, and increased mortality. Epidemiological studies have established these associations, and there ...are now numerous experimental and clinical studies which have provided information on the possible underlying mechanisms. Mechanistic proof-of-concept studies with surrogate endpoints have been performed to demonstrate that treatment of OSA by continuous positive airway pressure (CPAP) has the potential to reverse or at least to attenuate not only OSA but also the adverse cardiovascular effects associated with OSA. However, no randomized studies have been performed to demonstrate that treatment of OSA by CPAP improves clinical outcomes in patients with cardiovascular risk factors and/or established cardiovascular disease and concomitant OSA. In the present review, we summarize the current knowledge on the role of OSA as a potential cardiovascular risk factor, the impact of OSA on cardiac function, the role of OSA as a modifier of the course of cardiovascular diseases such as coronary artery disease, atrial fibrillation, and heart failure, and the insights from studies evaluating the impact of CPAP therapy on the cardiovascular features associated with OSA.
It is estimated that approximately 50% of the heart failure population has a normal left ventricular ejection fraction, a complex broadly referred to as heart failure with normal left ventricular ...ejection fraction (HFNEF). While these patients have been considered in epidemiologic studies and clinical trials to represent a single pool of patients, limited more detailed studies indicate that HFNEF patients are a very heterogeneous group, with a number of key pathophysiologic mechanisms. This review summarizes and critically analyzes available data on the pathophysiology of HFNEF, placing it into context with a recently developed diagnostic algorithm. We evaluate the utility of commonly applied echocardiographic measures and biomarkers and integrate mechanistic observations into potential future therapeutic directions.
Objectives The purpose of this study was to invasively investigate the hemodynamic response to exercise in patients with heart failure with normal ejection fraction (HFNEF) and to evaluate the ...ability of the peak early diastolic transmitral velocity to peak early diastolic annular velocity ratio (E/e′) to reflect exercise hemodynamics. Background There is little information regarding the hemodynamic response to exercise in HFNEF. Methods Patients with HFNEF (n = 14) and asymptomatic controls (n = 8) underwent right-side heart catheterization at rest and during supine cycle ergometer exercise and echocardiography with measurement of resting and peak exercise E/e′. Results Resting pulmonary capillary wedge pressure (PCWP) (10 ± 4 mm Hg vs. 10 ± 4 mm Hg; p = 0.94) was similar in HFNEF patients and controls, but stroke volume index (SVI) (p = 0.02) was lower, and systemic vascular resistance index (SVRI) (p = 0.01) was higher in patients. Patients stopped exercise at lower work rate (0.63 ± 0.29 W/kg vs. 1.13 ± 0.49 W/kg; p = 0.006). Although peak exercise PCWP was similar in both groups (23 ± 6 mm Hg vs. 20 ± 7 mm Hg; p = 0.31), the peak PCWP/work rate ratio was higher in patients compared with controls (46 ± 31 mm Hg/W/kg vs. 20 ± 9 mm Hg/W/kg; p = 0.03). Peak exercise SVI (p = 0.001) was lower and SVRI was higher (p = 0.01) in patients. Resting E/e′ was modestly elevated in patients (13.2 ± 4.1 vs. 9.5 ± 3.4; p = 0.04). Peak exercise E/e′ did not differ between the groups (11.1 ± 3.4 vs. 9.4 ± 3.4; p = 0.28). Conclusions The HFNEF patients achieved a similar peak exercise PCWP to that of asymptomatic controls, at a much lower workload. This occurs at a lower SVI and in the setting of higher SVRI. The E/e′ does not reflect the hemodynamic changes during exercise in HFNEF patients.
The ratio of tricuspid regurgitation velocity (TRV) to the time-velocity integral of the right ventricular outflow tract (TVIRVOT) has been studied as a reliable measure to distinguish elevated from ...normal pulmonary vascular resistance (PVR). The equation TRV/TVIRVOT × 10 + 0.16 (PVRecho) has been shown to provide a good noninvasive estimate of PVR. However, its role in patients with significantly elevated PVR (> 6 Wood units WU) has not been conclusively evaluated. The aim of this study was to establish the validity of the TRV/TVIRVOT ratio as a correlate of PVR. The role of TRV/TVIRVOT was also compared with that of a new ratio, TRV(2)/TVIRVOT, in patients with markedly elevated PVR (>6 WU).
Data from five validation studies using TRV/TVIRVOT as an estimate of PVR were compared with invasive PVR measurements (PVRcath). Multiple linear regression analyses were generated between PVRcath and both TRV/TVIRVOT and TRV(2)/TVIRVOT. Both PVRecho and a new derived regression equation based on TRV(2)/TVIRVOT: 5.19 × TRV(2)/TVIRVOT - 0.4 (PVRecho2) were compared with PVRcath using Bland-Altman analysis. Logistic models were generated, and cutoff values for both TRV/TVIRVOT and TRV(2)/TVIRVOT were obtained to predict PVR > 6 WU.
One hundred fifty patients remained in the final analysis. Linear regression analysis between PVRcath and TRV/TVIRVOT revealed a good correlation (r = 0.76, P < .0001, Z = 0.92). There was a better correlation between PVRcath and TRV(2)/TVIRVOT (r = 0.79, P < .0001, Z = -0.01) in the entire cohort as well as in patients with PVR > 6 WU. Moreover, PVRecho2 compared better with PVRcath than PVRecho using Bland-Altman analysis in the entire cohort and in patients with PVR > 6 WU. TRV(2)/TVIRVOT and TRV/TVIRVOT both predicted PVR > 6 WU with good sensitivity and specificity.
TRV/TVIRVOT is a reliable method to identify patients with elevated PVR. In patients with TRV/TVIRVOT > 0.275, PVR is likely > 6 WU, and PVRecho2 derived from TRV(2)/TVIRVOT provides an improved noninvasive estimate of PVR compared with PVRecho.
Elderly heart failure (HF) patients are assumed to prefer improved quality of life over longevity, but sufficient data are lacking. Therefore, we assessed the willingness to trade survival time for ...quality-of-life (QoL) and the preferences for resuscitation.
At baseline and after 12 and 18 months, 622 HF patients aged ≥60 years (77 ± 8 years, 74% NYHA-class ≥III) participating in the Trial of Intensified vs. standard Medical therapy in Elderly patients with Congestive Heart Failure had prospective evaluation of end-of-life preferences by answering trade-off questions (willingness to accept a shorter life span in return for living without symptoms) and preferences for resuscitation if necessary. The time trade-off question was answered by 555 patients (89%), 74% of whom were not willing to trade survival time for improved QoL. This proportion increased over time (Month 12: 85%, Month 18: 87%, P < 0.001). In multivariable analysis, willingness to trade survival time increased with age, female sex, a reduced Duke Activity Status Index, Geriatric Depression Score, and history of gout, exercise intolerance, constipation and oedema, but even combining these variables did not result in reliable prediction. Of 603 (97%) patients expressing their resuscitation preference, 51% wished resuscitation, 39% did not, and 10% were undecided, with little changes over time. In 430 patients resuscitation orders were known; they differed from patients' preferences 32% of the time. End-of-life preferences were not correlated to 18-month outcome.
Elderly HF patients are willing to address their end-of-life preferences. The majority prefers longevity over QoL and half wished resuscitation if necessary. Prediction of individual preferences was inaccurate.
Abstract
Introduction
Little is known about patients with acute myocardial infarction (AMI) and chronic lung disease (CLD). The aim of our study was to analyze risk factors, treatment, and outcome of ...AMI patients with CLD over the last 20 years using the nationwide AMIS Plus registry.
Methods
All AMI patients enrolled in the AMIS Plus registry with data on CLD between January 2002 and December 2021 were included. Chronic lung disease was determined according to the definition used in the Charlson Comorbidity Index. Data on baseline characteristics, regular medication, immediate therapy within 24 hours, in-hospital interventions and treatments, in-hospital outcome, complications and discharge medication were analyzed using descriptive statistics and logistic regression.
Results
Among 53,680 AMI patients, 5.8% had a CLD. The CLD group included 26.6% female and 73.4% male patients. Gender distribution was similar in patients with and without CLD. Patients with CLD were significantly older (71.2 vs. 65.8 y; p<0.001), more frequently diagnosed with NSTEMI, had more comorbidities and were less frequently never smokers (17.4% vs. 35.3%; p<0.001) compared to patients without CLD. In addition, CLD patients were less likely to receive aspirin, P2Y12 inhibitors, beta-blockers, ACE inhibitors and statins (all p<0.001), and were also less likely to undergo percutaneous coronary interventions (68.7% vs. 82.5%; p<0.001). Median length of stay was 2 days longer for CLD patients. Patients with CLD had more major adverse cardiac and cerebrovascular events in-hospital (10.3% vs. 5.9%; p<0.001) and higher crude in-hospital mortality (8.3% vs. 4.7%; p<0.001). However, multivariable regression analysis showed that CLD was not an independent predictor for in-hospital mortality (OR 1.19 (95% CI 0.98–1.45), p=0.081).
Conclusion
Patients with CLD were less likely to receive evidence-based medicine and had a worse in-hospital outcome compared to those without CLD. However, after adjustment, CLD was not an independent predictor of in-hospital mortality.
Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): AstraZeneca AG, Biotronik (Schweiz) AG
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