Background
Sodium–glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial ...(The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk.
Methods and Results
We randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add‐on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium‐82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate‐pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08–2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, −0.18 to 0.21) or placebo groups: 0.06 (95% CI, −0.15 to 0.27), with no treatment effect −0.05 (95% CI, −0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium‐82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A
1c
by 0.76% (95% CI, 1.0–0.5;
P
<0.001) and increased hematocrit by 1.69% (95% CI, 0.7–2.6;
P
<0.001).
Conclusions
Empagliflozin did not improve MFR among patients with type 2 diabetes mellitus and high cardiovascular disease risk. The present study does not support that short‐term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials.
Registration
URL:
https://clinicaltrialsregister.eu/
; Unique identifier: 2016‐003743‐10.
There is a paucity of data on heart transplantation (HTx) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), and specific recommendations on indications for listing ARVC ...patients for HTx are lacking. In order to delineate features pertinent to HTx assessment, we explored the pre-HTx characteristics and clinical history in a cohort of ARVC patients who received heart transplants.
Data from 31 ARVC/HTx patients enrolled in the Nordic ARVC Registry, transplanted between 1988 and 2014 at a median age of 46years (14–65), were compared with data from 152 non-transplanted probands with Definite ARVC according to 2010 Task Force Criteria from the same registry.
The HTx patients were younger at presentation, median 31 vs. 38years (p=0.001). There was no difference in arrhythmia-related events. The indication for HTx was heart failure in 28 patients (90%) and ventricular arrhythmias in 3 patients (10%). During median follow-up of 4.9years (0.04–28), there was one early death and two late deaths. Survival was 91% at 5years after HTx. Age at first symptoms under 35years independently predicted HTx in our cohort (OR=7.59, 95% CI 2.69–21.39, p<0.001).
HTx in patients with ARVC is performed predominantly due to heart failure. This suggests that current 2016 International Society for Heart and Lung Transplantation heart transplant listing recommendations for other cardiomyopathies could be applicable in many cases when taking into account the haemodynamic consequences of right ventricular failure in conjunction with ventricular arrhythmia.
Fixed pulmonary hypertension (FPH) is considered a contraindication to cardiac transplantation. Ventricular assist device (VAD) therapy through prolonged left ventricular unloading may reverse FPH. ...Our aim was to assess post-transplant outcomes and survival in patients with and without FPH undergoing VAD implantation as bridge to transplant.
Fifty-four patients received an intracorporeal left VAD (LVAD) as a bridge to transplant from 2000 to 2008 at two institutions (Rigshospitalet, Denmark, and the Toronto General Hospital, Canada). Twenty-two (41%) patients had fixed FPH (defined as pulmonary vascular resistance PVR >3 Wood units and resistant to pulmonary vasodilators) prior to VAD implant (FPH group) and were compared with 32 patients without FPH (NoFPH group). Baseline characteristics, pre- and post-transplant pulmonary pressures, incidence of complications and post-transplant survival were analyzed.
Baseline characteristics were similar except that patients in the FPH group were older (46 ± 11 years vs 39 ± 13 years in the NoFPH group, p < 0.05). The mean pre-VAD PVR was 4.3 ± 1.7 Wood units in the FPH group and 1.7 ± 0.5 Wood units in the NoFPH group (p < 0.001). Pulmonary pressures were higher in the FPH group immediately prior to VAD implant, but they were comparable immediately pre-transplant and during the first year post-transplant. The incidence of post-transplant RV failure was not significantly different between groups. Post-transplant survival was similar between groups.
VAD therapy successfully decreases pulmonary hypertension, even in patients with "fixed" FPH, allowing candidacy for heart transplantation. Among bridge-to-transplant candidates, the presence of FPH does not reduce post-transplant survival.
IntroductionPleural effusion is present in half of the patients hospitalised with acute heart failure. The condition is treated with diuretics and/or therapeutic thoracentesis for larger effusions. ...No evidence from randomised trials or guidelines supports thoracentesis to alleviate pleural effusion due to acute heart failure. The Thoracentesis to Alleviate cardiac Pleural effusion Interventional Trial (TAP-IT) will investigate if a strategy of referring patients with acute heart failure and pleural effusion to up-front thoracentesis by pleural pigtail catheter insertion in addition to pharmacological therapy compared with pharmacological therapy alone can increase the number of days the participants are alive and not hospitalised during the 90 days following randomisation.Methods and analysisTAP-IT is a pragmatic, multicentre, open-label, randomised controlled trial aiming to include 126 adult patients with left ventricular ejection fraction ≤45% and a non-negligible pleural effusion due to heart failure. Participants will be randomised 1:1, stratified according to site and anticoagulant treatment, and assigned to referral to up-front ultrasound-guided pleural pigtail catheter thoracentesis in addition to standard pharmacological therapy or to standard pharmacological therapy only. Thoracentesis is performed according to local guidelines and can be performed in participants in the pharmacological treatment arm if their condition deteriorates or if no significant improvement is observed within 5 days. The primary endpoint is how many days participants are alive and not hospitalised within 90 days from randomisation and will be analysed in the intention-to-treat population. Key secondary outcomes include 90-day mortality, complications, readmissions, and quality of life.Ethics and disseminationThe study has been approved by the Capital Region of Denmark Scientific Ethical Committee (H-20060817) and Knowledge Center for Data Reviews (P-2021–149). All participants will sign an informed consent form. Enrolment began in August 2021. Regardless of the nature, results will be published in a peer-reviewed medical journal.Trial registration numberNCT05017753.
Background Long-term clinical studies of peripartum cardiomyopathy ( PPCM ) are few. We aimed to measure the long-term effect of PPCM on cardiac function in comparison with the long-term effects of ...severe preeclampsia and uncomplicated pregnancy. Methods and Results A nationwide Danish cohort of women diagnosed with PPCM from 2005 to 2014 ( PPCM group) were invited to participate in a clinical follow-up study including maximal cardiopulmonary exercise testing and cardiac magnetic resonance imaging. Matched women with previous severe preeclampsia (preeclampsia group) and previous uncomplicated pregnancies (uncomplicated pregnancies group) served as comparison groups. A total of 84 women with 28 in each group participated. Median time to follow-up after PPCM was 91 months. Most women (85%) in the PPCM group reported no symptoms of heart failure. Mean left ventricular ejection fraction in the PPCM group was normal at 62%, but significantly lower than in the preeclampsia group and the uncomplicated pregnancies group where mean left ventricular ejection fraction was 69% and 67%, respectively ( P<0.0001). Women in the PPCM group also had impaired diastolic function with reduced left ventricular peak filling rate, left atrial passive emptying volume, and left atrial passive emptying fraction. Maximal exercise capacity (peak VO
) was also reduced in the PPCM group compared with the preeclampsia group and the uncomplicated pregnancies group, and PPCM , high body mass index, and low left ventricular ejection fraction independently predicted reduced peak VO
. Only 1 woman with PPCM had late gadolinium enhancement. Conclusions Women generally recovered left ventricular ejection fraction and were asymptomatic 7 years after PPCM , but had subtle diastolic dysfunction on cardiac magnetic resonance imaging and reduced peak VO
. Focal myocardial fibrosis assessed with late gadolinium enhancement was, however, uncommon.
Heart muscle cells produce peptide hormones such as natriuretic peptides. Developing hearts also express the gene for the classic intestinal hormone cholecystokinin (CCK) in amounts similar to those ...in the intestine and brain. However, cardiac expression of peptides other than natriuretic peptides has only been suggested using transcriptional measures or methods, with the post-translational phase of gene expression unaddressed. In this study, we examined the cardiac expression of the CCK gene in adult mammals and its expression at the protein level. Using quantitative PCR, a library of sequence-specific pro-CCK assays, peptide purification, and mass spectrometry, we demonstrate that the mammalian heart expresses pro-CCK in amounts comparable to natriuretic prohormones and processes it to a unique, triple-sulfated, and N-terminally truncated product distinct from intestinal and cerebral CCK peptides. Isoprenaline rapidly stimulated cardiac CCK gene expression in vitro and in vivo, which suggests that the cardiac-specific truncated pro-CCK may have pathophysiological relevance as a new marker of heart failure. The suggestion is confirmed by measurement of plasma from heart failure patients.
Background: Mammalian hearts express hormones such as natriuretic peptides.
Results: Cardiomyocytes also express the cholecystokinin gene at the protein level with unique precursor processing.
Conclusion: Cardiac expression of procholecystokinin is cell-specific, which differentiates the expression from that of intestinal endocrine cells and cerebral neurons.
Significance: Cardiomyocytes express not only natriuretic peptides but also known peptides in intestinal endocrine cells and cerebral neurons.
Patients with heart failure and chronic kidney disease (CKD) may have an increased risk of death from causes competing with arrhythmic death, which could have implications for the efficacy of ...implantable cardioverter-defibrillators (ICDs). We examined the long-term effects of primary prophylactic ICD implantation, compared with usual care, according to baseline CKD status in an extended follow-up study of DANISH (Danish Study to Assess the Efficacy of ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality).
In the DANISH trial, 1116 patients with nonischemic heart failure with reduced ejection fraction were randomized to receive an ICD (N=556) or usual care (N=550). Outcomes were analyzed according to CKD status (estimated glomerular filtration rate ≥/<60 mL/min per 1.73 m
) at baseline. In total, 1113 patients had an available estimated glomerular filtration rate measurement at baseline (median estimated glomerular filtration rate 73 mL/min per 1.73 m
), and 316 (28%) had CKD. During a median follow-up of 9.5 years, ICD implantation, compared with usual care, did not reduce the rate of all-cause mortality (no CKD, HR, 0.82 95% CI, 0.64-1.04; CKD, HR, 1.02 95% CI, 0.75-1.38;
=0.31) or cardiovascular death (no CKD, HR, 0.77 95% CI, 0.58-1.03; CKD, HR, 1.05 95% CI, 0.73-1.51;
=0.20), irrespective of baseline CKD status. Similarly, baseline CKD status did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (no CKD, HR, 0.57 95% CI, 0.32-1.00; CKD, HR, 0.65 95% CI, 0.34-1.24;
=0.70).
ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce the rate of sudden cardiovascular death, regardless of baseline kidney function in patients with nonischemic heart failure with reduced ejection fraction.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.
Aims
Transthyretin amyloid cardiomyopathy (ATTR‐CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a ...shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR‐CM, using multiple national health registers in Denmark, Finland, Norway, and Sweden.
Methods and results
Transthyretin amyloid cardiomyopathy patients were identified during 2008–2018 using a combination of diagnosis codes for amyloidosis and heart disease and were matched to patients with non‐ATTR heart failure (HF). An identical study design was used in each country to facilitate comparison and aggregation of results. A total of 1930 ATTR‐CM patients were identified from national health registers in the four countries. In 2018, prevalence of ATTR‐CM per 100 000 inhabitants ranged from 1.4 in Denmark to 5.0 in Sweden; a steep increase over time was observed in Sweden and Norway. Median survival from diagnosis was 30 months for ATTR‐CM patients and 67 months for matched HF patients. Survival was significantly lower for female than for male ATTR‐CM patients (median survival: 22 and 36 months), while no significant difference was observed in the HF cohort.
Conclusions
This study provides the first nationwide estimates of the prevalence, clinical characteristics, and mortality of patients with ATTR‐CM, using identical study design across several countries. Findings corroborate previous case series showing high mortality in ATTR‐CM, two‐fold higher than for other HF patients and higher in women than men, highlighting the need for more precise and early diagnosis to reduce the disease burden.
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