Aims
Decisive evidence on the optimal diuretic agent, dosing schedule, and administration route is lacking in acute heart failure (AHF) with congestion. The Acetazolamide in Decompensated heart ...failure with Volume OveRload (ADVOR) trial is designed to test the hypothesis that the carbonic anhydrase inhibitor acetazolamide, a potent inhibitor of proximal tubular sodium reabsorption, improves decongestion when combined with loop diuretic therapy in AHF, potentially leading to better clinical outcomes.
Methods
The ADVOR trial is set up as a multicentre, randomized, double‐blind, placebo‐controlled study, aiming to recruit 519 patients with AHF and clinically evident volume overload. All study participants receive high‐dose intravenous loop diuretics as background therapy and are randomized towards intravenous acetazolamide at a dose of 500 mg once daily vs. placebo, stratified according to including study centre and ejection fraction (< 40% vs. ≥ 40%). The primary endpoint is successful decongestion with no more than trace oedema assessed on the third morning after hospital admission, with good diuretic efficacy defined as a urine output > 3.5 L during the first 30–48 h of decongestive treatment. Secondary endpoints include all‐cause mortality or heart failure readmission after 3 months, length of hospital stay for the index admission, and longitudinal changes in the EuroQol‐5 dimensions questionnaire.
Conclusion
ADVOR will investigate if acetazolamide combined with loop diuretic therapy improves decongestion in AHF with volume overload.
In the context of the coronavirus disease 2019 pandemic, myocardial injury is a relatively frequent finding. Progression to cardiogenic shock has been rarely described, especially in healthy young ...patients. The underlying mechanisms are to date controversial. A previously healthy 18‐year‐old female teenager affected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) developed fulminant cardiogenic shock requiring a prompt extracorporeal membrane oxygenation support. Cardiac involvement was predominant compared with the pulmonary one. Myocardial biopsies were performed; and in order to clarify the pathophysiology of the acute heart failure, optical and transmission electron microscopy study was realized. Two additional immunohistology techniques were developed in order to (i) detect a SARS‐CoV‐2 recombinant fusion nucleoprotein by using a specific antibody and (ii) study fractalkine expression induced by activated endothelium because this molecule is well known to be elevated in patients with severe cytokine release syndrome. SARS‐CoV‐2 genome was not detected in the myocardium. Even if the clinical presentation, laboratory markers, and cardiac imaging techniques strongly suggested fulminant myocarditis, histology and immunohistology were not fully consistent with this diagnosis according to the Dallas criteria. Although rare suspected coronavirus particles were found by transmission electron microscopy in the cardiac endothelium, neither significant immunoreactivity for the viral nucleocapsid protein nor image suggestive of endotheliitis was detected. Intense endothelial immunoreactivity pattern for fractalkine expression was observed. From a clinical point of view, the left ventricular systolic function gradually improved, and the patient survived after a long stay in the intensive care unit. Our observations suggest that a massive cytokine storm induced by SARS‐CoV‐2 infection was the main cause of the cardiogenic shock, making a direct viral injury pathway very unlikely.
Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster ...decongestion in patients with acute decompensated heart failure with volume overload, is unclear.
In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed.
A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval CI, 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.
The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).
Cardiovascular disorders have been extensively reported during COVID-19 illness, including arrhythmias such as atrioventricular conduction disturbances. To date, one case of transient heart block has ...been reported after COVID-19 vaccine.
A 73 years-old woman presented with shortness of breath and fatigue 2 weeks after receiving her second dose of BNT162b2 SARS-CoV-2 mRNA vaccine. ECG showed complete AV block with normal narrow QRS complexes. Chronic treatment with Bisoprolol for hypertension was stopped but complete AV block persisted 48 hours thereafter. Therefore, a permanent pacemaker was implanted. Three months later, pacemaker follow-up revealed no ventricular stimulation, suggesting complete recovery of AV conduction, even after resumption of bisoprolol. Five months after the second dose, she received a third dose of the same vaccine. Three weeks later, she once again complained of dyspnea on exertion. ECG showed sinus rhythm with permanent ventricular stimulation. After device inhibition, complete AV block was confirmed and, 2 weeks later, conduction was restored once more.
It is known that vaccines can induce AV conduction disturbances, mostly reversible. The underlying mechanisms leading to high-degree AV block remain unclear and are probably multiple. Although being exceptional after COVID-19 vaccine, our case illustrates the fact that the latter can induce such a disturbance which may be transient and recurrent even in the absence of underlying conduction disorder.
COVID-19 vaccination may transitorily interfere with cardiac conduction system even in subjects without known underlying heart disease.
•Transient but recurrent complete AV block after COVID-19 vaccine.
Aims
Chronic heart failure (CHF) patients are frequently rehospitalized within 6 months after an episode of fluid retention. Rehospitalizations are preventable, but this requires an extensive ...organization of the healthcare system. In this study, we tested whether intensive follow‐up of patients through a telemonitoring‐facilitated collaboration between general practitioners (GPs) and a heart failure clinic could reduce mortality and rehospitalization rate.
Methods and results
One hunderd and sixty CHF patients mean age 76 ± 10 years, 104 males, mean left ventricular ejection fraction (LVEF) 35 ± 15% were block randomized by sealed envelopes and assigned to 6 months of intense follow‐up facilitated by telemonitoring (TM) or usual care (UC). The TM group measured body weight, blood pressure, and heart rate on a daily basis with electronic devices that transferred the data automatically to an online database. Email alerts were sent to the GP and heart failure clinic to intervene when pre‐defined limits were exceeded. All‐cause mortality was significantly lower in the TM group as compared with the UC group (5% vs. 17.5%, P = 0.01). The total number of follow‐up days lost to hospitalization, dialysis, or death was significantly lower in the TM group as compared with the UC group (13 vs. 30 days, P = 0.02). The number of hospitalizations for heart failure per patient showed a trend (0.24 vs. 0.42 hospitalizations/patient, P = 0.06) in favour of TM.
Conclusion
Telemonitoring‐facilitated collaboration between GPs and a heart failure clinic reduces mortality and number of days lost to hospitalization, death, or dialysis in CHF patients. These findings need confirmation in a large trial.
Trial registation: ISRCTN39223875
Aims
To describe the baseline characteristics of participants in the Acetazolamide in Decompensated Heart Failure with Volume Overload (ADVOR) trial and compare these with other contemporary diuretic ...trials in acute heart failure (AHF).
Methods and results
ADVOR recruited 519 patients with AHF, clinically evident volume overload, elevated N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and maintenance loop diuretic therapy prior to admission. All participants received standardized loop diuretics and were randomized towards once daily intravenous acetazolamide (500 mg) versus placebo, stratified according to study centre and left ventricular ejection fraction (LVEF) (≤40% vs. >40%). The primary endpoint was successful decongestion assessed by a dedicated score indicating no more than trace oedema and no other signs of congestion after three consecutive days of treatment without need for escalating treatment. Mean age was 78 years, 63% were men, mean LVEF was 43%, and median NT‐proBNP 6173 pg/ml. The median clinical congestion score was 4 with an EuroQol‐5 dimensions health utility index of 0.6. Patients with LVEF ≤40% were more often male, had more ischaemic heart disease, higher levels of NT‐proBNP and less atrial fibrillation. Compared with diuretic trials in AHF, patients enrolled in ADVOR were considerably older with higher NT‐proBNP levels, reflecting the real‐world clinical situation.
Conclusion
ADVOR is the largest randomized diuretic trial in AHF, investigating acetazolamide to improve decongestion on top of standardized loop diuretics. The elderly enrolled population with poor quality of life provides a good representation of the real‐world AHF population. The pragmatic design will provide novel insights in the diuretic treatment of patients with AHF.
Baseline characteristics of ADVOR trial participants. ACEi, angiotensin‐converting enzyme inhibitor; AHF, acute heart failure; ARB, angiotensin receptor blocker; IV, intravenous; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.
The TElemonitoring in the MAnagement of Heart Failure (TEMA-HF) 1 long-term follow-up study assessed whether an initial six-month telemonitoring (TM) programme compared with usual care (UC) would ...result in reduced all-cause mortality, heart failure admissions and healthcare costs in chronic heart failure (CHF) patients at long-term follow-up.
Of the 160 patients included in the multi-centre, randomised controlled telemonitoring trial (TEMA-HF 1, time point t
); 142 CHF patients (65% male; age: 76 ± 10 years; EF: 36 ± 15%) were alive and entered the follow-up study (time point: t
) with a final evaluation at 79 months (time point: t
). Both TM and UC group patients received standard heart failure care during the follow-up study (time points: t
- t
). The primary endpoint was all-cause mortality. Secondary outcomes included days lost due to heart failure readmissions and readmission/patient follow-up related healthcare costs.
Compared with usual care, the initial six-month TM programme had no significant effect on all-cause mortality (hazard ratio: 0.83; 95% confidence interval, 0.57 to 1.20; p = 0.32). The number of days lost due to heart failure readmissions was significantly lower in the TM group ( p = 0.04). Healthcare costs did not differ significantly between the TM (€ 9140 ± 10580) and UC group (€ 12495 ± 22433) ( p = 0.87).
An initial six-month telemonitoring programme was not associated with reduced all-cause mortality in CHF patients at long-term follow-up but resulted in a reduction in the number of days lost due to heart failure readmissions. This study is registered in the ClinicalTrials.gov registry (NCT03171038) (URL: https://clinicaltrials.gov/ct2/show/NCT03171038 ).
In the post-myocardial infarction phase, mortality risk is related to the severity of mitral regurgitation (MR). Ischemic MR is a dynamic condition that can be studied during exercise. Whether the ...assessment of exercise-induced changes in the degree of MR provides prognostic information is unknown.
Ninety-eight consecutive patients with chronic ischemic left ventricular dysfunction and at least mild MR who prospectively underwent quantitative measurement of the regurgitant volume and the effective regurgitant orifice (ERO) of MR at rest and during semisupine exercise test were followed up for 19+/-8 months. The 16 patients who underwent surgery were censored at the time of operation. Of the 82 patients who were medically treated, 9 (11%) died. No clinical data demonstrated a distinction between survivors and nonsurvivors. By multivariate Cox regression analysis, independent predictors of cardiac death were an increase in ERO by > or =13 mm2 (P=0.0045) during exercise, an ERO >20 mm2 at rest (P=0.01), and a shorter mitral deceleration time (P=0.044). Half of the patients with exercise-induced significant increases in MR who died had moderate MR at rest. In contrast, none of the 14 patients with a decrease in MR at exercise displayed cardiac death.
In patients with ischemic MR and left ventricular dysfunction, quantitative assessment of exercise-induced changes in the degree of MR provides independent prognostic information. Significant exercise-induced increases in MR unmask patients at high risk of poor outcome.
Heart failure (HF) constitutes the growing cardiovascular burden and the major public health issue, but comprehensive statistics on HF epidemiology and related management in Europe are missing. The ...Heart Failure Association (HFA) Atlas has been initiated in 2016 in order to close this gap, representing the continuity directly rooted in the European Society of Cardiology (ESC) Atlas of Cardiology. The major aim of the HFA Atlas is to establish a contemporary dataset on HF epidemiology, resources and reimbursement policies for HF management, organization of the National Heart Failure Societies (NHFS) and their major activities, including education and HF awareness. These data are gathered in collaboration with the network of NHFS of the ESC member and ESC affiliated countries. The dataset will be continuously improved and advanced based on the experience and enhanced understanding of data collection in the forthcoming years. This will enable revealing trends, disparities and gaps in knowledge on epidemiology and management of HF. Such data are highly needed by the clinicians of different specialties (aside from cardiologists and cardiac surgeons), researchers, healthcare policy makers, as well as HF patients and their caregivers. It will also allow to map the snapshot of realities in HF care, as well as to provide insights for evidence‐based health care policy in contemporary management of HF. Such data will support the ESC/HFA efforts to improve HF management ant outcomes through stronger recommendations and calls for action. This will likely influence the allocation of funds for the prevention, treatment, education and research in
HF.
We conducted a nationwide survey to describe the in-and out-of-hospital flow (diagnosis, treatment and follow-up) of patients with heart failure with reduced ejection fraction (HFrEF).
A survey was ...developed with five dedicated HF cardiologists. The data are all self-reported by cardiologists.
The response rate was 84%. Presence of a dedicated HF cardiologist or HF nurse was indicated by 49% and 46% of the hospitals respectively. Devices (p < .05), angiotensin receptor neprilysin inhibitors, and rehabilitation are considered more standard of care therapy by dedicated compared to non-dedicated HF cardiologists. Most cardiologists indicated that target dosages of HF drugs can be reached in 25‒75% of patients. Achieving >75% of the target dose seems easier for angiotensin converting enzyme inhibitor/angiotensin receptor blockers (ACEI/ARB) (22%) and mineralocorticoid receptor antagonists (25%), compared to β-blockers (10%) and angiotensin receptor neprilysin inhibitors (7%). 62%, 49% and 4% of the cardiologists indicated to use subtypes of angiotensin converting enzyme inhibitors, angiotensin receptor blockers and β-blockers respectively not validated in the HF population. In the acute setting, dedicated HF cardiologists (23%) are less influenced by blood parameters for decongestion compared to non-dedicated HF cardiologists (39%). They tend to change patients more to guideline-recommended drugs (60% vs 47%). Six minutes walk test and ergospirometry are significantly more used by dedicated compared to non-dedicated HF cardiologists for HF drug change (17% and 29% vs 2% and 4%).
This survey showed that a minority of hospitals have HF care. Those that do, report a higher implementation of guideline-recommended diagnosis, treatment and follow-up of HF patients. Competent authorities could use this survey as a tool to improve HF care.
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