Age differences of patients treated with wearable cardioverter defibrillator: Data from a multicentre registry.

BACKGROUND: Wearable cardioverter defibrillators (WCD) are used as a 'bridging' technology in patients, who are temporarily at high risk for sudden cardiac death (SCD). Several factors should be taken into consideration, for example patient selection, compliance and optimal drug treatment, when WCD is prescribed. We aimed to present real-world data from seven centres from Germany and Switzerland according to age differences regarding the outcome, prognosis, WCD data and compliance. MATERIALS AND METHODS: Between 04/2012 and 03/2021, 1105 patients were included in this registry. Outcome data according to age differences (old ≥45 years compared to young <45 years) were analysed. At young age, WCDs were more often prescribed due to congenital heart disease and myocarditis. On the other hand, ischaemic cardiomyopathy (ICM) was more present in older patients. Wear days of WCD were similar between both groups (p = .115). In addition, during the WCD use, documented arrhythmic life-threatening events were comparable [sustained ventricular tachycardia: 5.8% vs. 7.7%, ventricular fibrillation (VF) .5% vs. .6%] and consequently the rate of appropriate shocks was similar between both groups. Left ventricular ejection fraction improvement was documented over follow-up with a better improvement in younger patients as compared to older patients (77% vs. 63%, p = .002). In addition, at baseline, the rate of atrial fibrillation was significantly higher in the older age group (23% vs. 8%; p = .001). The rate of permanent cardiac implantable electronic device implantation (CiED) was lower in the younger group (25% vs. 36%, p = .05). The compliance rate defined as wearing WCD at least 20 h per day was significantly lower in young patients compared to old patients (68.9% vs. 80.9%, p < .001). During the follow-up, no significant difference regarding all-cause mortality or arrhythmic death was documented in both groups. A low compliance rate of wearing WCD is predicted by young patients and patients suffering from non-ischaemic cardiomyopathies. CONCLUSION: Although the compliance rate in different age groups is high, the average wear hours tended to be lower in young patients compared to older patients. The clinical events were similar in younger patients compared to older patients.

Incidence of atrial and ventricular arrhythmias in obese patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan.

AIM: To compare clinical outcomes among patients with heart failure and reduced ejection fraction (HFrEF) according to body mass index (BMI) after initiating treatment with an angiotensin-receptor neprilysin inhibitor (ARNI). METHODS: We gathered data from 2016 to 2020 at the University Medical Center Mannheim; 208 consecutive patients were divided into two groups according to BMI (< 30 kg/m2 ; n = 116, ≥ 30 kg/m2 ; n = 92). Clinical outcomes, including mortality rate, all-cause hospitalizations and congestion, were systematically analysed. RESULTS: At the 12-month follow-up, the mortality rate was similar in both groups (7.9% in BMI < 30 kg/m2 vs. 5.6% in BMI ≥ 30 kg/m2 ; P = .76). All-cause hospitalization before ARNI treatment was comparable in both groups (63.8% in BMI < 30 kg/m2 vs. 57.6% in BMI ≥ 30 kg/m2 ; P = .69). After ARNI treatment, the hospitalization rate was also comparable in both groups at the 12-month follow-up (52.2% in BMI < 30 kg/m2 vs. 53.7% in BMI ≥ 30 kg/m2 ; P = .73). Obese patients experienced more congestion compared with non-obese patients at follow-up, without statistical significance (6.8% in BMI < 30 kg/m2 vs. 15.5% in BMI ≥ 30 kg/m2 ; P = .11). Median left ventricular ejection fraction (LVEF) improved in both groups, but significantly more in non-obese compared with obese patients at the 12-month follow-up (from 26% [3%-45%] [min.-max.] vs. 29% [10%-45%] [min.-max.] [P = .56] to 35.5% [15%-59%] [min.-max.] vs. 30% [13%-50%] [min.-max.] [P = .03], respectively). The incidence of atrial fibrillation (AF), non-sustained (ns) and sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) was less in non-obese than in obese patients after initiation of sacubitril/valsartan at the 12-month follow-up (AF: 43.5% vs. 53.7%; P = .20; nsVT: 9.8% vs. 28.4%; P = .01; VT: 14.1% vs. 17.9%; P = .52; VF: 7.6% vs. 13.4%; P = .23). CONCLUSIONS: The incidence of congestion in obese patients was higher compared with non-obese patients. LVEF improved significantly more in non-obese compared with obese HFrEF patients. Furthermore, AF and the ventricular tachyarrhythmia rate were revealed more in obesity compared with those without obesity at the 12-month follow-up.

Does Albumin Predict the Risk of Mortality in Patients with Cardiogenic Shock?

This study investigates the prognostic impact of albumin levels in patients with cardiogenic shock (CS). Intensive care unit (ICU) related mortality in CS patients remains unacceptably high despite improvement concerning the treatment of CS patients. Limited data regarding the prognostic value of albumin in patients with CS is available. All consecutive patients with CS from 2019 to 2021 were included at one institution. Laboratory values were retrieved from the day of disease onset (day 1) and days 2, 3, 4, and 8 thereafter. The prognostic impact of albumin was tested for 30-day all-cause mortality. Moreover, the prognostic performance of albumin decline during ICU treatment was examined. Statistical analyses included univariable t-test, Spearman's correlation, Kaplan-Meier analyses, multivariable mixed analysis of variance (ANOVA), C-Statistics, and Cox proportional regression analyses. In total, 230 CS patients were included, with an overall all-cause mortality at 30 days of 54%. The median albumin on day 1 was 30.0 g/L. Albumin on day 1 was able to discriminate between 30-day survivors and non-survivors (area under the curve (AUC) 0.607; 0.535-0.680; p = 0.005). CS patients with albumin < 30.0 g/L were associated with an increased risk of 30-day all-cause mortality (63% vs. 46%; log-rank p = 0.016; HR = 1.517; 95% CI 1.063-2.164; p = 0.021), which was demonstrated even after multivariable adjustment. Moreover, a decrease of albumin levels by ≥20% from day 1 to day 3 was accompanied by a higher risk of 30-days all-cause mortality (56% vs. 39%; log-rank p = 0.036; HR = 1.645; 95% CI 1.014-2.669; p = 0.044). Especially when combined with lactate, creatinine, and cardiac troponin I, reliable discrimination of 30-day all-cause mortality was observed, including albumin in CS risk stratification models (AUC = 0.745; 95% CI 0.677-0.814; p = 0.001). In conclusion, low baseline albumin levels as well as a decay of albumin levels during the course of ICU treatment, deteriorate prognostic outcomes in CS patients. The additional assessment of albumin levels may further improve risk stratification in CS patients.

Thalassaemia is paradoxically associated with a reduced risk of in-hospital complications and mortality in COVID-19: Data from an international registry.

Although numerous patient-specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalassaemic syndromes in COVID-19 patients remains poorly understood. We studied the outcomes of 137 COVID-19 patients with a history of transfusion-dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalassaemia. The mean age of thalassaemia patients included in our study was 41 ± 16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 40% of thalassaemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID-19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age-, sex- and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in-hospital complications (supplemental oxygen use, admission to an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassaemia group compared to the matched cohort with no history of thalassaemia. Amongst thalassaemia patients in general, the TIT group exhibited a higher rate of hospitalization compared to the TDT group (p = 0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the TIT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in-hospital, all-cause mortality, whereas the presence of thalassaemia (either TDT or TIT) was found to be independently associated with reduced all-cause mortality. The presence of thalassaemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models.

Sex differences and adherence of patients treated with wearable cardioverter-defibrillator: Insights from an international multicenter register.

AIMS: Treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden cardiac death (SCD) as a bridging therapy until a cardioverter-defibrillator may be implanted. We analyzed in a multicenter setting a consecutive patient cohort wearing WCD to explore sex differences. METHODS AND RESULTS: We analyzed 708 consecutive patients, 579 (81.8%) from whom were males and 129 (18.2%) females (age, 60.5 ± 14 vs. 61.6 ± 17 years old; p = .44). While the rate of ischemic cardiomyopathy (ICM) as a cause of prescription of WCD was significantly higher in males as compared to females (42.7% vs. 26.4%; p = .001), females received it more frequently due to nonischemic cardiomyopathy (NICM) (55.8% vs. 42.7%); p = .009). The wear time of WCD was equivalent in both groups (21.1 ± 4.3 h/days in males vs. 21.5 ± 4.4 h/days in females; p = .27; and 62.6 ± 44.3 days in males vs. 56.5 ± 39 days in females; p = .15). Mortality was comparable in both groups at 2-year-follow-up (6.8% in males vs. 9.7% in females; p = .55). Appropriate WCD shocks and the incidence of ICD implantations were similar in both groups (2.4% in males vs. 3.9% in females; p = .07) (35.1% in males vs. 31.8% in females; p = .37), respectively. In age tertile analysis, compliance was observed more in 73-91 years old group as compared with 14-51 years old group (87.8% vs. 68.3%; p < .001). CONCLUSION: Compliance for wearing WCD was excellent regardless of sex. Furthermore, mortality and the incidence of ICD implantations were comparable in both sexes. Appropriate WCD shocks were similar in both sexes.

Fever following Covid-19 vaccination in subjects with Brugada syndrome: Incidence and management.

BACKGROUND: Fever is a potential side effect of the Covid-19 vaccination. Patients with Brugada syndrome (BrS) have an increased risk of life-threatening arrhythmias when experiencing fever. Prompt treatment with antipyretic drugs is suggested in these patients. AIM OF THE STUDY: To evaluate the incidence and management of fever within 48 h from Covid-19 vaccination among BrS patients. METHODS: One hundred sixty-three consecutive patients were enrolled in a prospective registry involving five European hospitals with a dedicated inherited disease ambulatory. RESULTS: The mean age was 50 ± 14 years and 121 (75%) patients were male. Prevalence of Brugada electrocardiogram (ECG) pattern type-1, -2, and -3 was 32%, 44%, and 24%, respectively. Twenty-eight (17%) patients had an implantable cardioverter-defibrillator (ICD). Fever occurred in 32 (19%) BrS patients after 16 ± 10 h from vaccination, with a peak of body temperature of 37.9° ± 0.5°. Patients with fever were younger (39 ± 13 vs. 48 ± 13 years, p = .04). No additional differences in terms of sex and cardiovascular risk factors were found between patients with fever and not. Twenty-seven (84%) out of 32 patients experienced mild fever and five (16%) moderate fever. Pharmacological treatment with antipyretic drugs was required in 18 (56%) out of 32 patients and was associated with the resolution of symptoms. No patient required hospital admission and no arrhythmic episode was recorded in patients with ICD within 48 h after vaccination. No induced type 1 BrS ECG pattern and new ECG features were found among patients with moderate fever. CONCLUSION: Fever is a common side effect in BrS patients after the Covid-19 vaccination. Careful evaluation of body temperature and prompt treatment with antipyretic drugs may be needed.

Digitalis therapy in patients with ventricular tachyarrhythmias.

Objective. The study sought to assess the prognostic value of treatment with digitalis on long-term prognosis in patients with ventricular tachyarrhythmias and atrial fibrillation (AF) and/or heart failure (HF). Background. Data regarding the outcome of digitalis therapy following ventricular tachyarrhythmias is limited. Methods. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with digitalis were compared to patients without. The primary prognostic endpoint was all-cause mortality at 3 years, secondary endpoints comprised a composite arrhythmic endpoint (i.e. recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies, sudden cardiac death) and cardiac rehospitalization. Kaplan Mayer survival curves, multivariable cox regression, and time trend analyses were applied for statistics. Results. Eight hundred and thirty-one patients were included (20% treated with digitalis and 80% without). At 3 years, digitalis treatment was not associated with all-cause mortality following ventricular tachyarrhythmias (24 vs. 21%, log-rank p = .736; HR = 1.063; 95% CI 0.746-1.515; p = .736). However, digitalis therapy was associated with an increased risk of the composite arrhythmic endpoint (38 vs. 23%; log-rank p = .001; HR = 1.719; 95% CI 1.279-2.311; p = .001) and cardiac rehospitalization (31 vs. 18%; log-rank p = .001; HR = 1.829; 95% CI 1.318-2.538; p = .001), which was still evident within multivariable Cox regression analyses. Finally, digitoxin may be associated with a worse prognosis than digoxin. Conclusion. Digitalis therapy was not associated with mortality in patients with ventricular tachyarrhythmias, but with increased risk of the composite arrhythmic endpoint and cardiac rehospitalization at 3 years.

Prognostic value of beta-blocker doses in patients with ventricular tachyarrhythmias.

The study investigates the prognostic significance of beta-blocker (BB) dose in patients with ventricular tachyarrhythmias. Limited data regarding the prognostic impact of BB dose in ventricular tachyarrhythmias is available. A large retrospective registry was used including consecutive patients on BB treatment with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Discharge BB doses were grouped as > 0-12.5%, > 12.5-25%, > 25-50%, and > 50% according to doses used in randomized trials. The primary endpoint was all-cause mortality at three years. Secondary endpoints comprised of a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias and appropriate ICD therapies) and cardiac rehospitalization. Kaplan-Meier survival curves and multivariable Cox regression analyses were applied for statistics. A total of 1313 patients with BB were included; most patients were discharged with > 25-50% of BB target dose (59%). At three years, > 12.5-25% of BB target dose was associated with improved long-term mortality as compared to the > 0-12.5% group (HR = 0.489; 95% CI 0.297-0.806; p = 0.005), whereas higher BB doses did not improve survival (> 25-50%: HR = 0.849; p = 0.434; > 50%: HR = 0.735; p = 0.285). In contrast, the composite endpoint and risk of rehospitalization were not affected by BB target dose. In conclusion, > 12.5-25% of BB target dose is associated with best long-term survival among patients with ventricular tachyarrhythmias. In contrast, risk of the composite arrhythmic endpoint and risk of cardiac rehospitalization were not affected by BB dose.

Effect of Mineralocorticoid Receptor Antagonists on the Prognosis of Patients with Ventricular Tachyarrhythmias.

INTRODUCTION: The study sought to assess the effect of treatment with mineralocorticoid receptor antagonists (MRAs) on long-term prognosis of patients with systolic heart failure (HF) surviving index episodes of ventricular tachyarrhythmias. METHODS: A large retrospective registry was used including consecutive HF patients with left ventricular ejection fraction <45% and index episodes of ventricular tachyarrhythmias from 2002 to 2015. The primary endpoint was all-cause mortality at 3 years and secondary endpoints were rehospitalization, as well as the composite endpoint consisting of recurrent ventricular tachyarrhythmias, sudden cardiac death and appropriate implantabe cardioverter defibrillator (ICD) therapies at 3 years. RESULTS: 748 patients were included, 20% treated with MRA and 80% without. At 3 years, treatment with MRA was not associated with improved all-cause mortality (22% vs. 24%, log-rank p = 0.968; hazard ratio (HR) = 1.008; 95% CI 0.690-1.472; p = 0.968). Accordingly, risk of the composite endpoint (28% vs. 27%; HR = 1.131; 95% CI 0.806-1.589; p = 0.476) and first cardiac rehospitalization (24% vs. 22%; HR = 1.139; 95% CI 0.788-1.648; p = 0.489) were not affected by treatment with MRA. CONCLUSION: In patients with ventricular tachyarrhythmias, treatment with MRA was not associated with improved all-cause mortality at 3 years. The therapeutic effect of MRA treatment in patients with ventricular tachyarrhythmias needs to be reinvestigated within further randomized controlled trials.

QTc Interval Prolongation and Life-Threatening Arrhythmias During Hospitalization in Patients With Coronavirus Disease 2019 (COVID-19): Results From a Multicenter Prospective Registry.

BACKGROUND: Prolonged QTc intervals and life-threatening arrhythmias (LTA) are potential drug-induced complications previously reported with antimalarials, antivirals, and antibiotics. Our objective was to evaluate the prevalence and predictors of QTc interval prolongation and incidences of LTA during hospitalization for coronavirus disease 2019 (COVID-19) among patients with normal admission QTc. METHODS: We enrolled 110 consecutive patients in a multicenter international registry. A 12-lead electrocardiograph was performed at admission, after 7, and at 14 days; QTc values were analyzed. RESULTS: After 7 days, 15 (14%) patients developed a prolonged QTc (pQTc; mean QTc increase 66 ± 20 msec; +16%; P < .001); these patients were older and had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, and lower platelet counts. The QTc increase was inversely proportional to the baseline QTc level and leukocyte count and directly proportional to the basal heart rate (P < .01).We conducted a multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate, and dual antiviral therapy; age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00-1.13; P < .05), basal heart rate (OR, 1.07; 95% CI, 1.02-1.13; P < .01), and dual antiviral therapy (OR, 12.46; 95% CI, 2.09-74.20; P < .1) were independent predictors of QT prolongation.The incidence rate of LTA during hospitalization was 3.6%. There was 1 patient who experienced cardiac arrest and 3 with nonsustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of the mortality rate. CONCLUSIONS: After 7 days of hospitalization, 14% of patients with COVID-19 developed pQTc; age, basal heart rate, and dual antiviral therapy were found to be independent predictors of pQTc. Life-threatening arrhythmias have an incidence rate of 3.6%, and were associated with a poor outcome.

Renin-angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: Final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry.

BACKGROUND: The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site. METHODS: HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications. RESULTS: We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p<0.05 for all). However, we did not find differences regarding the hospital use of RASi and the development of heart failure. CONCLUSION: RASi historic use, at admission, is not related to an adjusted worse prognosis in hospitalized COVID-19 patients, although it points out a high-risk population. In this setting, the in-hospital prescription of RASi is associated with improved survival and fewer short-term complications.

COVID-19 and the impact of arterial hypertension-An analysis of the international HOPE COVID-19 Registry (Italy-Spain-Germany).

BACKGROUND: A systematic analysis of concomitant arterial hypertension in COVID-19 patients and the impact of angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID-19 in presence and absence of arterial hypertension. MATERIALS AND METHODS: Out of 5837 COVID-19 patients, 2850 (48.8%) patients had the diagnosis arterial hypertension. 1978/2813 (70.3%) patients were already treated with ACEI or ARBs. The clinical outcome of the present subanalysis included all-cause mortality over 40 days of follow-up. RESULTS: Patients with arterial hypertension suffered significantly more from different complications including respiratory insufficiency (60.8% vs 39.5%), heart failure (9.9% vs 3.1%), acute kidney injury (25.3% vs 7.3%), pneumonia (90.6% vs 86%), sepsis (14.7% vs 7.5%), and bleeding events (3.6% vs 1.6%). The mortality rate was 29.6% in patients with concomitant arterial hypertension and 11.3% without arterial hypertension (P < .001). Invasive and non-invasive respiratory supports were significantly more required in presence of arterial hypertension as compared without it. In the multivariate cox regression analysis, while age≥65, benzodiazepine, antidepressant at admission, elevated LDH or creatinine, respiratory insufficiency and sepsis might be a positive independent predictors of mortality, antiviral drugs, interferon treatment, ACEI or ARBs at discharge or oral anticoagulation at discharge might be an independent negative predictor of the mortality. CONCLUSIONS: The mortality rate and in-hospital complications might be increased in COVID-19 patients with a concomitant history of arterial hypertension. The history of ACEI or ARBs treatments does not seem to impact the outcome of these patients.

Clinical profile and predictors of in-hospital mortality among older patients hospitalised for COVID-19.

BACKGROUND: the coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and mortality, particularly in older patients. METHODS: post hoc analysis of the international, multicentre, 'real-world' HOPE COVID-19 registry. All patients aged ≥65 years hospitalised for COVID-19 were selected. Epidemiological, clinical, analytical and outcome data were obtained. A comparative study between two age subgroups, 65-74 and ≥75 years, was performed. The primary endpoint was all cause in-hospital mortality. RESULTS: about, 1,520 patients aged ≥65 years (60.3% male, median age of 76 [IQR 71-83] years) were included. Comorbidities such as hypertension (69.2%), dyslipidaemia (48.6%), cardiovascular diseases (any chronic heart disease in 38.4% and cerebrovascular disease in 12.5%), and chronic lung disease (25.3%) were prevalent, and 49.6% were on ACEI/ARBs. Patients aged 75 years and older suffered more in-hospital complications (respiratory failure, heart failure, renal failure, sepsis) and a significantly higher mortality (18.4 vs. 48.2%, P < 0.001), but fewer admissions to intensive care units (11.2 vs. 4.8%). In the overall cohort, multivariable analysis demonstrated age ≥75 (OR 3.54), chronic kidney disease (OR 3.36), dementia (OR 8.06), peripheral oxygen saturation at admission <92% (OR 5.85), severe lymphopenia (<500/mm3) (OR 3.36) and qSOFA (Quick Sequential Organ Failure Assessment Score) >1 (OR 8.31) to be independent predictors of mortality. CONCLUSION: patients aged ≥65 years hospitalised for COVID-19 had high rates of in-hospital complications and mortality, especially among patients 75 years or older. Age ≥75 years, dementia, peripheral oxygen saturation <92%, severe lymphopenia and qSOFA scale >1 were independent predictors of mortality in this population.

Non-invasive ventilation for SARS-CoV-2 acute respiratory failure: a subanalysis from the HOPE COVID-19 registry.

BACKGROUND: The COVID-19 pandemic has seriously challenged worldwide healthcare systems and limited intensive care facilities, leading to physicians considering the use of non-invasive ventilation (NIV) for managing SARS-CoV-2-related acute respiratory failure (ARF). METHODS: We conducted an interim analysis of the international, multicentre HOPE COVID-19 registry including patients admitted for a confirmed or highly suspected SARS-CoV-2 infection until 18 April 2020. Those treated with NIV were considered. The primary endpoint was a composite of death or need for intubation. The components of the composite endpoint were the secondary outcomes. Unadjusted and adjusted predictors of the primary endpoint within those initially treated with NIV were investigated. RESULTS: 1933 patients who were included in the registry during the study period had data on oxygen support type. Among them, 390 patients (20%) were treated with NIV. Compared with those receiving other non-invasive oxygen strategy, patients receiving NIV showed significantly worse clinical and laboratory signs of ARF at presentation. Of the 390 patients treated with NIV, 173 patients (44.4%) met the composite endpoint. In-hospital death was the main determinant (147, 37.7%), while 62 patients (15.9%) needed invasive ventilation. Those requiring invasive ventilation had the lowest survival rate (41.9%). After adjustment, age (adjusted OR (adj(OR)) for 5-year increase: 1.37, 95% CI 1.15 to 1.63, p<0.001), hypertension (adj(OR) 2.95, 95% CI 1.14 to 7.61, p=0.03), room air O2 saturation <92% at presentation (adj(OR) 3.05, 95% CI 1.28 to 7.28, p=0.01), lymphocytopenia (adj(OR) 3.55, 95% CI 1.16 to 10.85, p=0.03) and in-hospital use of antibiotic therapy (adj(OR) 4.91, 95% CI 1.69 to 14.26, p=0.003) were independently associated with the composite endpoint. CONCLUSION: NIV was used in a significant proportion of patients within our cohort, and more than half of these patients survived without the need for intubation. NIV may represent a viable strategy particularly in case of overcrowded and limited intensive care resources, but prompt identification of failure is mandatory to avoid harm. Further studies are required to better clarify our hypothesis. TRIAL REGISTRATION NUMBERS: NCT04334291/EUPAS34399.

Obesity Paradox in Heart Failure with Mildly Reduced Ejection Fraction.

Objective: The study investigates the prognostic impact of body mass index (BMI) in patients hospitalized with heart failure with mildly reduced ejection fraction (HFmrEF). Background: Limited data regarding the prognostic impact of BMI in patients with HFmrEF is available. Methods: Consecutive patients with HFmrEF (ie, left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. Risk stratification was performed according to WHO-defined BMI groups. The primary endpoint was all-cause mortality at 30 months (median follow-up). Kaplan-Meier, uni- and multivariable Cox proportional regression analyses were applied for statistics. Results: 1832 consecutive patients with HFmrEF were included with a median BMI of 26.7 kg/m2 (IQR 24.0-30.8 kg/m2). Patients with lowest BMI (ie, 18.5-24.9 kg/m2) were associated with highest risk of all-cause mortality at 30 months compared to patients with higher BMI values (40.0% vs 29.0% vs 21.4% vs 20.9%; log rank p = 0.001; HR = 0.721; 95% CI 0.656-0.793; p = 0.001). Even after multivariable adjustment, higher BMI values were associated with improved survival at 30 months (HR = 0.963; 95% CI 0.943-0.985; p = 0.001). In contrast, the risk of HF- related rehospitalization at 30 months was not affected by BMI (log rank p = 0.064). Conclusion: In patients hospitalized with HFmrEF, lower BMI was associated with increased risk of all-cause mortality at 30 months, suggesting an obesity paradox in HFmrEF.

Prognostic Implications of Septal Hypertrophy in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

Cardiac remodeling is frequently observed in patients with heart failure (HF) and serves as an indicator of disease progression and severity. Septal hypertrophy represents an aspect of remodeling that can be easily assessed via an echocardiographic measurement of the interventricular septal end diastole (IVSd), but it has not been evaluated for its prognostic value, particularly in patients with heart failure with mildly reduced ejection fraction (HFmrEF). We retrospectively included 1881 consecutive patients hospitalized with HFmrEF (i.e., a left ventricular ejection fraction of 41-49% and signs and/or symptoms of HF) at one institution during a study period from 2016 to 2022. Septal hypertrophy, defined as an IVSd > 12 mm, was prevalent in 34% of the HFmrEF patients. Although septal hypertrophy was not associated with all-cause mortality at 30 months (median follow-up) (HR = 1.067; 95% CI: 0.898-1.267; p = 0.460), it was associated with an increased risk of hospitalization due to worsening HF at 30 months (HR = 1.303; 95% CI: 1.008-1.685; p = 0.044), which was confirmed even after multivariable adjustment (HR = 1.340; 95% CI: 1.002-1.792; p = 0.049) and propensity score matching (HR = 1.399; 95% CI: 1.002-1.951; p = 0.048). Although septal hypertrophy was not associated with the risk of all-cause mortality in patients with HFmrEF, it was identified as an independent predictor of long-term HF-related rehospitalization.

Prognostic impact of prior LVEF in patients with heart failure with mildly reduced ejection fraction.

AIMS: As there is limited evidence regarding the prognostic impact of prior left ventricular ejection fraction (LVEF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF), this study investigates the prognostic impact of longitudinal changes in LVEF in patients with HFmrEF. METHODS: Consecutive patients with HFmrEF (i.e. LVEF 41-49% with signs and/or symptoms of HF) were included retrospectively in a monocentric registry from 2016 to 2022. Based on prior LVEF, patients were categorized into three groups: stable LVEF, improved LVEF, and deteriorated LVEF. The primary endpoint was 30-months all-cause mortality (median follow-up). Secondary endpoints included in-hospital and 12-months all-cause mortality, as well as HF-related rehospitalization at 12 and 30 months. Kaplan-Meier and multivariable Cox proportional regression analyses were applied for statistics. RESULTS: Six hundred eighty-nine patients with HFmrEF were included. Compared to their prior LVEF, 24%, 12%, and 64% had stable, improved, and deteriorated LVEF, respectively. None of the three LVEF groups was associated with all-cause mortality at 12 (p ≥ 0.583) and 30 months (31% vs. 37% vs. 34%; log rank p ≥ 0.376). In addition, similar rates of 12- (p ≥ 0.533) and 30-months HF-related rehospitalization (21% vs. 23% vs. 21%; log rank p ≥ 0.749) were observed. These findings were confirmed in multivariable regression analyses in the entire study cohort. CONCLUSION: The transition from HFrEF and HFpEF towards HFmrEF is very common. However, prior LVEF was not associated with prognosis, likely due to the persistently high dynamic nature of LVEF in the follow-up period.

Effect of Heart Failure Pharmacotherapies in Patients with Heart Failure with Mildly Reduced Ejection Fraction.

OBJECTIVE: The study sought to comprehensively investigate the effect of heart failure (HF) pharmacotherapies in patients with heart failure with mildly reduced ejection fraction (HFmrEF). BACKGROUND: In the absence of randomized controlled trials, guideline recommendations concerning HF-related therapies in patients with HFmrEF are limited. METHODS: Consecutive patients hospitalized with HFmrEF were retrospectively included at one institution from 2016 to 2022. The prognostic value of treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitors, receptor blockers or receptor-neprilysin inhibitor (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA) and sodium-glucose transport protein 2 inhibitors (SGLT2i) was investigated for all-cause mortality at 30 months (median follow-up) and HF-related rehospitalization. RESULTS: 2,109 patients with HFmrEF were included. Treatment with BB (27.0% vs. 35%; HR = 0.737; 95% CI 0.617-0.881; p = 0.001), ACEi/ARB/ARNI (25.9% vs. 37.6%; HR = 0.612; 95% CI 0.517-0.725; p = 0.001) and SGLT2i (11.9% vs. 29.5%; HR = 0.441; 95% CI 0.236-0.824; p = 0.010) was associated with lower risk of 30-months all-cause mortality, which was still demonstrated after multivariable adjustment and propensity score matching. In contrast, MRA treatment was not associated with long-term prognosis. The risk of HF-related rehospitalization was not affected by HF pharmacotherapies. Finally, the lowest risk of long-term all-cause mortality was observed in patients with combined use of BB, ACEi/ARB/ARNI and SGLT2i (HR = 0.456; 95% CI 0.227-0.916; p = 0.027). CONCLUSION: BB, ACEi/ARB/ARNI and SGLT2i were independently associated with lower risk of all-cause mortality in patients with HFmrEF, specifically when applied as combined "HF triple therapy". Randomized studies are needed to investigate the effect of HF-related pharmacotherapies in patients with HFmrEF.

Although heart failure with mildly reduced ejection fraction (HFmrEF) affects one out of four patients with heart failure (HF), limited evidence regarding HF pharmacotherapies for the treatment of patients with HFmrEF is available. The present study investigates the treatment with beta-blockers (BB), angiotensin-converting enzyme inhibitors, receptor blockers or receptor-neprilysin inhibitor (ACEi/ARB/ARNI), mineralocorticoid receptor antagonists (MRA) and sodium-glucose transport protein 2 inhibitors (SGLT2i) on long-term outcomes using a large registry-based dataset of 2,109 patients hospitalized with HFmrEF. Treatment with BB, ACEi/ARB/ARNI and SGLT2i was independently associated with a lower risk of long-term all-cause mortality, even after multivariable adjustment and propensity score matching, specifically when applied in combination. In contrast, MRA treatment was not associated with outcomes in the present study. The present study supports the evidence that patients with HFmrEF may benefit from HF pharmacotherapies similar than patients with HF with reduced ejection fraction (HFrEF).

The impact of diabetes mellitus on the outcome of troponin-positive patients with non-obstructive coronary arteries.

Background: Diabetes mellitus is a major cardiovascular risk factor for the development of coronary artery disease, but knowledge about the impact of diabetes mellitus on the outcome of patients with myocardial infarction with non-obstructive coronary arteries is limited. The aim of this study was to investigate the prognostic impact of diabetes mellitus on in- and out-of-hospital adverse events in troponin-positive patients with non-obstructive coronary arteries. Methods and Results: A total of 373 troponin-positive patients with non-obstructive coronary arteries between 2010 and 2021 at Bergmannsheil University Hospital Bochum were enrolled, including 65 diabetics and 307 nondiabetics. The median follow-up was 6.2 years. The primary study end point was a composite of in-hospital major adverse cardiovascular events (MACE). Secondary endpoints covered MACE during follow-up.Mean age of the study cohort was 62.9 years and 49.3 % were male. Although the overall rate of in-hospital MACE was higher in diabetics (41.5 %) than in non-diabetics (33.9 %), this difference did not reach statistical significance (p = 0.240). The in-hospital mortality rate was low in both groups, 0 % of diabetes group versus 2.9 % of non-diabetic patients. During follow-up, diabetic patients had a significantly higher rate of MACE (51.9 % vs. 31.1 %, p = 0.004) and a significantly higher all-cause mortality rate than non-diabetic patients (42.3 % vs. 20.1 %, p < 0.001). Conclusion: Our study reveals that the impact of diabetes mellitus on cardiovascular outcomes in troponin-positive patients with non-obstructive coronary arteries intensifies over the long term, leading to increased rates of both cardiovascular adverse events and overall mortality.