Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure in elderly patients: A sub-analysis of the STRONG-HF randomized clinical trial.

AIMS: STRONG-HF examined a high-intensity care (HIC) strategy of rapid up-titration of guideline-directed medical therapy (GDMT) and close follow-up after acute heart failure (AHF) admission. We assess the role of age on efficacy and safety of HIC. METHODS AND RESULTS: Hospitalized AHF patients, not treated with optimal GDMT were randomized to HIC or usual care. The primary endpoint of 180-day death or HF readmission occurred equally in older (>65 years, n = 493, 74 ± 5 years) and younger patients (53 ± 11 years, adjusted hazard ratio [aHR] 1.02, 95% confidence interval [CI] 0.73-1.43, p = 0.89). Older patients received slightly lower GDMT to day 21, but same doses at day 90 and 180. The effect of HIC on the primary endpoint was numerically higher in younger (aHR 0.51, 95% CI 0.32-0.82) than older patients (aHR 0.73, 95% CI 0.46-1.15, adjusted interaction p = 0.30), partially related to COVID-19 deaths. After exclusion of COVID-19 deaths, the effect of HIC was similar in younger (aHR 0.51, 95% CI 0.32-0.82) and older patients (aHR 0.63, 95% CI 0.32-1.02, adjusted interaction p = 0.56), with no treatment-by-age interaction (interaction p = 0.57). HIC induced larger improvements in quality of life to day 90 in younger (EQ-VAS adjusted-mean difference 5.51, 95% CI 3.20-7.82) than in older patients (1.77, 95% CI -0.75 to 4.29, interaction p = 0.032). HIC was associated with similar rates of adverse events in older and younger patients. CONCLUSION: High-intensity care after AHF was safe and resulted in a significant reduction of all-cause death or HF readmission at 180 days across the study age spectrum. Older patients have smaller benefits in terms of quality of life.

Heart failure: an update from the last years and a look at the near future.

In the last years, major progress occurred in heart failure (HF) management. Quadruple therapy is now mandatory for all the patients with HF with reduced ejection fraction. Whilst verciguat is becoming available across several countries, omecamtiv mecarbil is waiting to be released for clinical use. Concurrent use of potassium-lowering agents may counteract hyperkalaemia and facilitate renin-angiotensin-aldosterone system inhibitor implementations. The results of the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trial were confirmed by the Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (DELIVER) trial, and we now have, for the first time, evidence for treatment of also patients with HF with preserved ejection fraction. In a pre-specified meta-analysis of major randomized controlled trials, sodium-glucose co-transporter-2 inhibitors reduced all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in the patients with HF regardless of left ventricular ejection fraction. Other steps forward have occurred in the treatment of decompensated HF. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload (ADVOR) trial showed that the addition of intravenous acetazolamide to loop diuretics leads to greater decongestion vs. placebo. The addition of hydrochlorothiazide to loop diuretics was evaluated in the CLOROTIC trial. Torasemide did not change outcomes, compared with furosemide, in TRANSFORM-HF. Ferric derisomaltose had an effect on the primary outcome of CV mortality or HF rehospitalizations in IRONMAN (rate ratio 0.82; 95% confidence interval 0.66-1.02; P = 0.070). Further options for the treatment of HF, including device therapies, cardiac contractility modulation, and percutaneous treatment of valvulopathies, are summarized in this article.

Machine learning for prediction of in-hospital mortality in coronavirus disease 2019 patients: results from an Italian multicenter study.

BACKGROUND: Several risk factors have been identified to predict worse outcomes in patients affected by SARS-CoV-2 infection. Machine learning algorithms represent a novel approach to identifying a prediction model with a good discriminatory capacity to be easily used in clinical practice. The aim of this study was to obtain a risk score for in-hospital mortality in patients with coronavirus disease infection (COVID-19) based on a limited number of features collected at hospital admission. METHODS AND RESULTS: We studied an Italian cohort of consecutive adult Caucasian patients with laboratory-confirmed COVID-19 who were hospitalized in 13 cardiology units during Spring 2020. The Lasso procedure was used to select the most relevant covariates. The dataset was randomly divided into a training set containing 80% of the data, used for estimating the model, and a test set with the remaining 20%. A Random Forest modeled in-hospital mortality with the selected set of covariates: its accuracy was measured by means of the ROC curve, obtaining AUC, sensitivity, specificity and related 95% confidence interval (CI). This model was then compared with the one obtained by the Gradient Boosting Machine (GBM) and with logistic regression. Finally, to understand if each model has the same performance in the training and test set, the two AUCs were compared using the DeLong's test. Among 701 patients enrolled (mean age 67.2 ±â€Š13.2 years, 69.5% male individuals), 165 (23.5%) died during a median hospitalization of 15 (IQR, 9-24) days. Variables selected by the Lasso procedure were: age, oxygen saturation, PaO2/FiO2, creatinine clearance and elevated troponin. Compared with those who survived, deceased patients were older, had a lower blood oxygenation, lower creatinine clearance levels and higher prevalence of elevated troponin (all P < 0.001). The best performance out of the samples was provided by Random Forest with an AUC of 0.78 (95% CI: 0.68-0.88) and a sensitivity of 0.88 (95% CI: 0.58-1.00). Moreover, Random Forest was the unique model that provided similar performance in sample and out of sample (DeLong test P = 0.78). CONCLUSION: In a large COVID-19 population, we showed that a customizable machine learning-based score derived from clinical variables is feasible and effective for the prediction of in-hospital mortality.

High troponin levels in patients hospitalized for coronavirus disease 2019: a maker or a marker of prognosis?

AIMS: Controversial data have been published regarding the prognostic role of cardiac troponins in patients who need hospitalization because of coronavirus disease 2019 (COVID-19). The aim of the study was to assess the role of high-sensitivity troponin plasma levels and of respiratory function at admission on all-cause deaths in unselected patients hospitalized because of COVID-19. METHODS: We pooled individual patient data from observational studies that assessed all-cause mortality of unselected patients hospitalized for COVID-19. The individual data of 722 patients were included. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) and high-sensitivity troponins was reported at admission in all patients. This meta-analysis was registered on PROSPERO (CRD42020213209). RESULTS: After a median follow-up of 14 days, 180 deaths were observed. At multivariable regression analysis, age [hazard ratio (HR) 1.083, 95% confidence interval (CI) 1.061-1.105, P < 0.0001], male sex (HR 2.049, 95% CI 1.319-3.184, P = 0.0014), moderate-severe renal dysfunction (estimated glomerular filtration rate  < 30 mL/min/m2) (HR 2.108, 95% CI 1.237-3.594, P = 0.0061) and lower PaO2/FiO2 (HR 0.901, 95% CI 0.829-0.978, P = 0.0133) were the independent predictors of death. A linear increase in the HR was associated with decreasing values of PaO2/FiO2 below the normality threshold. On the contrary, the HR curve for troponin plasma levels was near-flat with large CI for values above the normality thresholds. CONCLUSION: In unselected patients hospitalized for COVID-19, mortality is mainly driven by male gender, older age and respiratory failure. Elevated plasma levels of high-sensitivity troponins are not an independent predictor of worse survival when respiratory function is accounted for.

Determinants of the protective effect of glucocorticoids on mortality in hospitalized patients with COVID-19: Insights from the Cardio-COVID-Italy multicenter study.

BACKGROUND: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality. METHODS: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality. RESULTS: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26-0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO2/FiO2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO2/FiO2 ratio (<300), lower oxygen saturation (<90%), and higher CRP (>100 mg/L). CONCLUSIONS: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation.

ST-Segment-Elevation Myocardial Infarction During COVID-19 Pandemic: Insights From a Regional Public Service Healthcare Hub.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has led to a fast and radical transformation in social, economic, and healthcare networks. COVID-19 outbreak may thus have profound indirect consequences on clinical presentation and management of patients with ST-segment-elevation myocardial infarction (STEMI). Aim of this study was to assess clinical features of patients with STEMI during COVID-19 pandemic. METHODS: This single-center, prospective study from a regional public service healthcare hub in Milan included all consecutive patients with STEMI admitted to our institute from February 21 to April 1, 2020 (during COVID-19 pandemic). These patients were compared with a historical cohort of patients admitted for STEMI during the analogous time period (February 21 to April 1) in 2018 and 2019, in terms of time from symptoms onset to hospital admission, clinical characteristics, and in-hospital outcomes. RESULTS: A total of 26 patients were admitted for STEMI during the study period, and 7 (26.9%) of these patients tested positive for severe acute respiratory syndrome coronavirus 2. On admission, medical therapy, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers use, was similar between cohorts. Median (interquartile range) time from symptoms onset to hospital admission was significantly longer in 2020 as compared to the historical cohort (15.0 [2.0-48.0] versus 2.0 [1.0-3.0] hours; P<0.01). A higher proportion of patients presenting with late presentation STEMI was observed in 2020 compared with the historical cohort (50.0% versus 4.8%; P<0.01). Primary percutaneous coronary intervention resulted indicated in 80.8% of patients in 2020 compared with 100% in the historical cohort (P=0.06). In-hospital death, thromboembolism, mechanical ventilation, or hemodynamic decompensation needing inotropic or mechanical support were similar between years. CONCLUSIONS: These preliminary results from a cardiovascular regional public service healthcare hub demonstrate a significantly longer time from symptoms onset to hospital admission among patients with STEMI during COVID-19 pandemic compared with the same time period in the previous 2 years.

Pulmonary hypertension and right ventricular involvement in hospitalised patients with COVID-19.

OBJECTIVE: To assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). METHODS: This single-centre, observational, cross-sectional study included 211 patients with COVID-19 admitted to non-ICU departments who underwent a single transthoracic echocardiography (TTE). Patients with poor acoustic window (n=11) were excluded. Clinical, imaging, laboratory and TTE findings were compared in patients with versus without PH (estimated systolic pulmonary artery pressure >35 mm Hg) and with versus without RVD (tricuspid annular plane systolic excursion <17 mm or S wave <9.5 cm/s). The primary endpoint was in-hospital death or ICU admission. RESULTS: A total of 200 patients were included in the final analysis (median age 62 (IQR 52-74) years, 65.5% men). The prevalence of PH and RVD was 12.0% (24/200) and 14.5% (29/200), respectively. Patients with PH were older and had a higher burden of pre-existing cardiac comorbidities and signs of more severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (radiological lung involvement, laboratory findings and oxygenation status) compared with those without PH. Conversely, patients with RVD had a higher burden of pre-existing cardiac comorbidities but no evidence of more severe SARS-CoV-2 infection compared with those without RVD. The presence of PH was associated with a higher rate of in-hospital death or ICU admission (41.7 vs 8.5%, p<0.001), while the presence of RVD was not (17.2 vs 11.7%, p=0.404). CONCLUSIONS: Among hospitalised non-ICU patients with COVID-19, PH (and not RVD) was associated with signs of more severe COVID-19 and with worse in-hospital clinical outcome. TRIAL REGISTRATION NUMBER: NCT04318366.

Heart and Lung Multimodality Imaging in COVID-19.

The severe acute respiratory syndrome-coronavirus-2 outbreak has rapidly reached pandemic proportions and has become a major threat to global health. Although the predominant clinical feature of coronavirus disease-2019 (COVID-19) is an acute respiratory syndrome of varying severity, ranging from mild symptomatic interstitial pneumonia to acute respiratory distress syndrome, the cardiovascular system can be involved in several ways. As many as 40% of patients hospitalized with COVID-19 have histories of cardiovascular disease, and current estimates report a proportion of myocardial injury in patients with COVID-19 of up to 12%. Multiple pathways have been suggested to explain this finding and the related clinical scenarios, encompassing local and systemic inflammatory responses and oxygen supply-demand imbalance. From a clinical point of view, cardiac involvement during COVID-19 may present a wide spectrum of severity, ranging from subclinical myocardial injury to well-defined clinical entities (myocarditis, myocardial infarction, pulmonary embolism, and heart failure), whose incidence and prognostic implications are currently largely unknown because of a significant lack of imaging data. Integrated heart and lung multimodality imaging plays a central role in different clinical settings and is essential in the diagnosis, risk stratification, and management of patients with COVID-19. The aims of this review are to summarize imaging-oriented pathophysiological mechanisms of lung and cardiac involvement in COVID-19 and to provide a guide for integrated imaging assessment in these patients.