To assess the interaction between heart failure (HF) severity and optimal reduction of secondary mitral regurgitation (SMR) on mortality in patients undergoing transcatheter edge-to-edge repair (M-TEER). Among 1656 patients included in the Italian Society of Interventional Cardiology (GIse) registry Of Transcatheter treatment of mitral valve regurgitaTiOn (GIOTTO) 984 had SMR and complete data on advanced HF. Advanced HF was defined as NYHA class III or IV, left ventricular ejection fraction ≤ 30

PURPOSE:Cardiogenic shock still has a high mortality. In order to correctly manage these patients, it is useful to have available haemodynamic parameters, invasive and non-invasive. The aim of this review is to show the current evidence on the use of echocardiographic aortic flow assessment by left ventricular outflow tract - velocity time integral. METHODS:Publications relevant to the discussion of echocardiographic aortic flow assessment by left ventricular outflow tract - velocity time integral and cardiogenic shock, were retrieved from PubMed®. RESULTS:Left ventricular outflow tract - velocity time integral is an easily sampled and reproducible parameter that has already been shown to have prognostic value in various cardiovascular pathologies, including myocardial infarction and heart failure. Although there are still few data available in the literature, the LVOT-VTI also seems to have an important role in CS from prognosis to guidance in the escalation/de-escalation of vasoactive therapy and to support devices by allowing an estimate of patient's probability of response to fluid administration. CONCLUSION:Aortic flow assessment can become a very useful invasive parameter in the management of cardiogenic shock.

BACKGROUND Risk stratification for transcatheter edge-to-edge mitral valve repair (TEER) is paramount in the decision-making process for treating severe mitral regurgitation (MR). OBJECTIVES This study sought to create and validate a user-friendly score (MitraScore) to predict the risk of mortality in patients undergoing TEER. METHODS The derivation cohort was based on a multicentric international registry that included 1,119 patients referred for TEER between 2012 and 2020. Score discrimination was assessed using Harrell's c-statistic, and the calibration was evaluated with the Gronnesby and Borgan goodness-of -fit test. An external validation was carried out in 725 patients from the GIOTTO registry. RESULTS After multivariate analysis, we identified 8 independent predictors of mortality during the follow-up (2.1 +/- 1.8 years): age $75 years, anemia, glomerular filtrate rate <60 mL/min/1.73 m2, left ventricular ejection fraction <40%, peripheral artery disease, chronic obstructive pulmonary disease, high diuretic dose, and no therapy with reninangiotensin system inhibitors. The MitraScore was derived by assigning 1 point to each independent predictor. The c-statistic was 0.70. Per each point of the MitraScore, the relative risk of mortality increased by 55% (HR: 1.55; 95% CI: 1.44-1.67; P < 0.001). The discrimination and calibration for mortality prediction was better than those of EuroSCORE II (c-statistic 0.61) or Society of Thoracic Surgeons score (c-statistic 0.57). The MitraScore maintained adequate performance in the validation cohort (c-statistic 0.66). The score was also predictive for heart failure rehospitalization and was correlated with the probability of clinical improvement. CONCLUSIONS The MitraScore is a simple prediction algorithm for the prediction of follow-up mortality in patients treated with TEER. (c) 2022 by the American College of Cardiology Foundation.

Background: COAPT-trial entry criteria are useful to identify patients with better outcomes after transcatheter edge-to-edge repair (TEER). However, up to one-half of real-world patients with secondary mitral regurgitation (SMR) undergoing TEER do not meet these highly selective criteria and no study has formally investigated them. The aim of this study was to evaluate the predictors of good outcome after TEER in COAPT-ineligible patients.Methods: All consecutive patients with SMR and heart failure (HF) treated with MitraClip at 3 European centres were retrospectively screened. The presence of at least 1 COAPT exclusion criterion was used to define a COAPT-ineligible profile, allowing the inclusion in the study population. Freedom from all-cause death or HF hospitalisation was evaluated at 2-year follow-up (primary end point).Results: A total of 305 patients (47%) had a COAPT-ineligible profile. An overall 58% rate of all-cause death or HF hospitalisation was detected at 2 years. Patients with a single COAPT exclusion criterion experienced fewer adverse events than those with multiple criteria (55% vs 69%). At multivariable Cox regression analysis, New York Heart Association functional class II, younger age (< 75 years), lower serum creatinine (< 2 mg/dL), lower left ventricular end-diastolic volume (< 240 mL), and the absence of hemodynamic instability, atrial fibrillation, and chronic obstructive pulmonary disease were independently associated with good outcome.Conclusions: In this real-world series of patients with SMR undergoing TEER, a COAPT-ineligible profile was common. The presence of only 1 COAPT exclusion criterion or the absence of hemodynamic instability were associated with the most favourable outcomes.

AimsThe HFA‐PEFF and H2FPEF scores have been developed to diagnose heart failure with preserved ejection fraction (HFpEF), and hold prognostic value. Their value in patients with HFpEF caused by cardiac amyloidosis (CA) has never been investigated.Methods and resultsWe evaluated the diagnostic and prognostic value of the HFA‐PEFF and H2FPEF scores in 304 patients from three cohorts with HFpEF caused by transthyretin CA (n = 160, 53%) or immunoglobulin light‐chain CA (n = 144, 47%). A diagnosis of HFpEF was more likely using the HFA‐PEFF score with 2 (1%), 71 (23%), and 231 (76%) patients ranked as having a low (0–1), intermediate (2–4), or high (5, 6) probability of HFpEF, respectively. Conversely, 36 (12%), 179 (59%) and 89 (29%) of patients ranked as having a low (0–1), intermediate (2–5), or high (6–9) probability of HFpEF using the H2FPEF score. During a median follow‐up of 19 months (interquartile range 8–40), 132 (43%) patients died. The HFA‐PEFF score, but not the H2FPEF score, predicted a high risk of all‐cause death which remained significant after adjustment for age, AL‐CA diagnosis, high‐sensitivity troponin T, N‐terminal pro‐B‐type natriuretic peptide, and echocardiographic parameters, including left ventricular global longitudinal strain, left ventricular diastolic function and right ventricular function (hazard ratio 1.51, 95% confidence interval 1.16–1.95, p = 0.002 for every 1‐point increase in HFA‐PEFF).ConclusionsThe HFA‐PEFF score has a higher diagnostic utility in HFpEF caused by CA and holds independent prognostic value for all‐cause mortality, while the H2FPEF score does not.

Abstract Aims To describe the characteristics of a cohort of patients with cardiac amyloidosis (CA) and to compare the two most common phenotypes of CA, transthyretin (ATTR) and immunoglobulin light-chain (AL). Methods and results One-hundred and eighty patients [n = 115 (64%) men, 74 ± 11 years] were retrospectively included from January 2013 to April 2021 in a single centre in Northern Italy. The majority [n = 102 (57%)] had ATTR-CA, whereas 78 patients (43%) had AL-CA. ATTR-CA patients were older (79 ± 7 vs. 66 ± 10 years, P < 0.001) and with higher prevalence of cardiovascular comorbidities, compared to those with AL-CA. ATTR-CA patients had higher N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and troponin levels, and lower haemoglobin and estimated glomerular filtration rate. Echocardiographic findings suggested a more advanced stage of the disease in the ATTR-CA subgroup [left ventricular ejection fraction (LVEF), 51 ± 10% vs. 60 ± 9%; global longitudinal strain (GLS), −11 ± 3% vs. −13 ± 4%; peak systolic wall motion velocity, 4.9 ± 1.7 vs. 6.4 ± 1.9; left ventricular mass index (LVMI) 316 ± 133 g/m2 vs. 157 ± 72 g/m2; left atrium volume index (LAVI) 48 ± 17 ml vs. 40 ± 16 ml; right ventricular diameter 31 ± 9 mm vs. 22 ± 5 mm; tricuspidal annular plane systolic excursion (TAPSE) 17 ± 5 vs. 19 ± 5; all P < 0.05). During a median follow-up of 15 (6–31) months, 68 (38%) patients died. All-cause death occurred in 31% vs. 46% patients with ATTR- and AL-CA, respectively. AL-CA was an independent predictor of mortality (adjusted hazard ratio 2.62, 95% confidence interval 1.55–4.43; P < 0.001). Other independent predictors of mortality were age, systolic blood pressure, Nt-proBNP, troponin and GLS. When cardiovascular (CV) death was considered, there was no significant difference between the two phenotypes (log rank P = 0.384). Conclusions Despite ATTR-CA patients showed worse baseline characteristics, suggesting a more advanced disease at presentation, AL-CA phenotype was associated with a higher risk of all-cause death. Of note, CV mortality was comparable between the two groups.

Abstract Aims An increasing number of patients with heart failure (HF) progresses to an advanced stage, characterized by persistent and sever symptoms and worse prognosis. A detailed characterization of patients with advanced HF is needed to optimize clinical management and timely refer for heart transplant or left ventricular assist device implantation. Methods and results A retrospective analysis was performed on patients with HF who were admitted to hospital or performed an outpatient visit at our centre (Spedali Civili di Brescia, Brescia, Italy) from 1 January 2020 to 31 December 2020, and who had at least one of the following high-risk characteristics: (1) previous or ongoing requirement for inotropes; (2) persisting New York Heart Association (NYHA) class III or IV and/or persistently high natriuretic peptides (BNP or NT-proBNP); (3) end-organ dysfunction, defined as worsening renal or liver dysfunction in the setting of HF; (4) ejection fraction (EF) <20%; (5) recurrent appropriate defibrillator shocks; (6) more than 1 hospitalization for HF in the last year; (7) persisting fluid overload and/or increasing diuretic requirement; (8) consistently low blood pressure (systolic blood pressure <90–100 mmHg); and (9) inability to up-titrate or need to decrease/cease HF therapies, such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor-neprilysin inhibitors, or mineralocorticoid receptor antagonists. The updated 2018 Heart Failure Association (HFA)—European Society of Cardiology (ESC) criteria for defining advanced HF were evaluated. The primary endpoint was all-cause mortality; secondary endpoints were a composite of all-cause mortality or hospitalization for HF and a composite of all-cause mortality or hospitalization for any reason. Among 493 patients with HF who were hospitalized or performed an outpatient visit in 2020, 230 (46.7%) had at least one high risk criterion and were included in the study. Mean age was 75.5 ± 11.9 years, 156 patients (67.8%) were men, and 160 patients (69.6%) were hospitalized and included as inpatients. Median EF was 38% [interquartile range (IQR): 25–50%] and 117 patients (50.9%) had HF with reduced EF (<40%); median NT-proBNP was 4044 (IQR: 2262–7664) pg/mL. Among the included 230 patients, 38 (16.5%) had all four updated HFA-ESC criteria defining advanced HF, 53 (23.0%) had American College of Cardiology (ACC)/American Heart Association (AHA) stage D, 21 (9.1%) had INTERMACS profile 1–3. In-hospital mortality was 10.6% (among inpatients). After a median follow-up of 301 (214–442) days, a total of 62 patients died (27.0%), and the secondary endpoints of all-cause death or HF hospitalization and all-cause death or any hospitalization were observed in 107 (46.5%) and 139 (60.4%) patients, respectively. Patients fulfilling all four updated HFA-ESC criteria for advanced HF had a higher risk of all-cause mortality (unadjusted HR: 2.06; 95% CI: 1.18–3.60; P = 0.011), also after adjustment for covariates of interest (adjusted HR: 2.20; 95% CI: 1.03, 4.70; P = 0.041). Conclusions In our contemporary, real-world cohort of HF patients with high-risk characteristics, mid-term prognosis was poor, and the use of updated HFA-ESC criteria defining advanced HF identified a subset at increased risk of mortality.

Left ventricle thrombus is considered a rare complication of Takotsubo syndrome. However, both a stress condition predisposing to Takotsubo syndrome and coagulation abnormalities coexist in COVID-19. We describe a case of a patient with COVID-19 with Takotsubo syndrome. (Level of Difficulty: Intermediate.).

Aims The aim of this study was to report the prevalence, clinical features and outcomes of patients with ST-elevation myocardial infarction (STEMI) hospitalized during the Corona-Virus Disease 2019 (COVID-19) outbreak compared with those admitted in a previous equivalent period. Methods and results Eighty-five patients admitted for STEMI at a high-volume Italian centre were included. Patients hospitalized during the COVID-19 outbreak (21 February–10 April 2020) (40%) were compared with those admitted in pre-COVID-19 period (3 January–20 February 2020) (60%). A 43% reduction in STEMI admissions was observed during the COVID-19 outbreak compared with the previous period. Time from symptom onset to first medical contact (FMC) and time from FMC to primary percutaneous coronary intervention (PPCI) were longer in patients admitted during the COVID-19 period compared with before [148 (79–781) versus 130 (30–185) min; P = 0.018, and 75 (59–148)] versus 45 (30–70) min; P < 0.001]. High-sensitive troponin T levels on admission were also higher. In-hospital mortality was 12% in the COVID-19 phase versus 6% in the pre-COVID-19 period. Incidence of the composite end-point, including free-wall rupture, severe left ventricular dysfunction, left ventricular aneurysm, severe mitral regurgitation and pericardial effusion, was higher during the COVID-19 than the pre-COVID-19 period (19.6 versus 41.2%; P = 0.030; odds ratio = 2.87; 95% confidence interval 1.09–7.58). Conclusion The COVID-19 pandemic had a significant impact on the STEMI care system reducing hospital admissions and prolonging revascularization time. This translated into a worse patient prognosis due to more STEMI complications.

Importance Virus infection has been widely described as one of the most common causes of myocarditis. However, less is known about the cardiac involvement as a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objective To describe the presentation of acute myocardial inflammation in a patient with coronavirus disease 2019 (COVID-19) who recovered from the influenzalike syndrome and developed fatigue and signs and symptoms of heart failure a week after upper respiratory tract symptoms. Design, Setting, and Participant This case report describes an otherwise healthy 53-year-old woman who tested positive for COVID-19 and was admitted to the cardiac care unit in March 2020 for acute myopericarditis with systolic dysfunction, confirmed on cardiac magnetic resonance imaging, the week after onset of fever and dry cough due to COVID-19. The patient did not show any respiratory involvement during the clinical course. Exposure Cardiac involvement with COVID-19. Main Outcomes and Measures Detection of cardiac involvement with an increase in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, echocardiography changes, and diffuse biventricular myocardial edema and late gadolinium enhancement on cardiac magnetic resonance imaging. Results An otherwise healthy 53-year-old white woman presented to the emergency department with severe fatigue. She described fever and dry cough the week before. She was afebrile but hypotensive; electrocardiography showed diffuse ST elevation, and elevated high-sensitivity troponin T and NT-proBNP levels were detected. Findings on chest radiography were normal. There was no evidence of obstructive coronary disease on coronary angiography. Based on the COVID-19 outbreak, a nasopharyngeal swab was performed, with a positive result for SARS-CoV-2 on real-time reverse transcriptase-polymerase chain reaction assay. Cardiac magnetic resonance imaging showed increased wall thickness with diffuse biventricular hypokinesis, especially in the apical segments, and severe left ventricular dysfunction (left ventricular ejection fraction of 35%). Short tau inversion recovery and T2-mapping sequences showed marked biventricular myocardial interstitial edema, and there was also diffuse late gadolinium enhancement involving the entire biventricular wall. There was a circumferential pericardial effusion that was most notable around the right cardiac chambers. These findings were all consistent with acute myopericarditis. She was treated with dobutamine, antiviral drugs (lopinavir/ritonavir), steroids, chloroquine, and medical treatment for heart failure, with progressive clinical and instrumental stabilization. Conclusions and Relevance This case highlights cardiac involvement as a complication associated with COVID-19, even without symptoms and signs of interstitial pneumonia.

BACKGROUND Under-reporting of clinical trial results inhibits dissemination of knowledge, limits understanding of therapeutic interventions, and may ultimately harm patients. OBJECTIVES This study examined the rates and predictors of heart failure clinical trial publication and how they have changed over time. METHODS This study assessed cross-sectional analysis of all heart failure clinical trials registered on ClinicalTrials.gov with at least 2 years follow-up after trial completion. The content area was chosen for the robust clinical trial activity in the field. The primary outcome was manuscript publication with multivariable proportional hazards adjustment to identify associations with publication. RESULTS Of the 1,429 included studies, 806 (56%) were published as manuscripts, 623 were unpublished, and 97 (7%) reported results without manuscript publication. Of the total, 1,243 were completed after 2007, when the mean 1-year publication rate for interventional trials rose from 12.7% to 19.6% (p = 0.049), which was possibly associated with changes in government regulation. However, there was no further sustained improvement over time, and there was no multivariable association between later completion dates and reporting or publication of results. Funding from the National Institutes of Health and use of clinical (death, hospitalization, myocardial infarction, changes in functional classification) rather than nonclinical primary endpoints were associated with earlier publication. Whether the results were consistent with the primary study hypothesis was not associated with likelihood of publication. CONCLUSIONS The rates of heart failure clinical trial publication or reporting of results remain unacceptably low. Additional efforts by all stakeholders, including investigators, sponsors, regulators, societies, editors, and journals are needed to improve data dissemination. (C) 2020 by the American College of Cardiology Foundation.

AIMS:The aim of this study was to evaluate the prognostic role of echocardiographic parameters assessing secondary mitral regurgitation (SMR) severity and left ventricular dimension, including proportionate versus disproportionate SMR, in MitraClip recipients. METHODS AND RESULTS:We analysed 137 patients undergoing MitraClip implantation for SMR at three centres. SMR was classified as proportionate or disproportionate based on the median value of the ratio between effective regurgitant orifice area (EROA) and left ventricular end-diastolic volume (LVEDV). The primary endpoint was a composite of cardiovascular mortality and heart failure hospitalisation at two-year follow-up. Mean age was 70±10 years, 80% were male, and median EuroSCORE II was 5.7%. No differences were observed in the disproportionate compared to the proportionate group except for a more severe NYHA class and their expected higher EROA and lower LVEDV. Number of clips deployed, device success and procedural success were similar between the two groups. Residual mitral regurgitation (MR) >1+ at 30 days was more common among patients with an EROA >0.42 cm2 compared to those with an EROA ≤0.42 cm2 (81.3% vs 58%; p=0.004). The relative risk of the primary endpoint was independent from any echocardiographic parameter, including the presence of disproportionate SMR. The only independent predictors of clinical events were EuroSCORE II >8%, NYHA class and residual MR >1+ at 30 days. CONCLUSIONS:Echocardiographic parameters, including the EROA/LVEDV ratio, do not have independent prognostic value in patients undergoing MitraClip implantation. High surgical risk, advanced symptoms and non-optimal MR reduction increase the relative risk of two-year clinical events.

AbstractAimsAcute heart failure (AHF) leads to a drastic increase in mortality and rehospitalization. The aim of the study was to identify prognostic variables in a real‐life population of AHF patients admitted to the emergency department with acute shortness of breath.Methods and resultsWe evaluated potential predictors of mortality in 728 consecutive patients admitted to the emergency department with AHF. Possible predictors of all‐cause and cardiovascular (CV) mortality were investigated by Cox and Fine and Gray models at multivariable analysis. Among the 728 patients, 256 died during the entire follow‐up, 142 of these due to CV cause. The 1 year mortality rate was 20%, with the highest risk of death during the index hospitalization (with 8% estimate in‐hospital mortality at 30 days). A higher risk of events during the index hospitalization was more evident for the CV deaths, for which we found a cumulative 1 year incidence of 12% with a cumulative incidence in the first 30 days of hospitalization of about 5%. At multivariable analysis, age (P < 0.001), New York Heart Association (NYHA) class IV vs. I–II–III (P = 0.001), systolic blood pressure (P < 0.001), non‐cardiac co‐morbidities (≥3 vs. 0, P = 0.05), oxygen saturation (P = 0.03), serum creatinine (P < 0.001), and left ventricular ejection fraction (LVEF) (40–49% vs. <40%, P = 0.004; ≥50% vs. <40%, P = 0.003) were independent predictors of all‐cause mortality during the entire follow‐up. Age (P = 0.03), systolic blood pressure (P = 0.01), oxygen saturation (P = 0.03), serum creatinine (P = 0.02), and LVEF (40–49% vs. <40%, P = 0.03; ≥50% vs. <40%, P = 0.004) were independent predictors of CV mortality during the entire follow‐up. NYHA class IV vs. I–II–III (P < 0.001), serum creatinine (P = 0.01), and LVEF (40–49% vs. <40%, P = 0.02; ≥50% vs. <40%, P < 0.001) remained independent predictors for in‐hospital death, while only serum creatinine (P = 0.04), LVEF (40–49% vs. <40%: 0.32, P = 0.04; ≥50% vs. <40%, P < 0.001), and NYHA class vs. I–II–III (P = 0.02) remained predictors for in‐hospital CV mortality.ConclusionsIn this real‐life cohort of patients with AHF, the results showed a similar mortality rate comparing with other analysis and with the most important registries. Age, NYHA class IV, systolic blood pressure, creatinine levels, sodium levels, and ejection fraction were independent predictors of 1 year mortality, while LVEF <40% was the only predictor of both all‐cause mortality and CV mortality.

Depression is a frequent and debilitating comorbidity that affects heart failure (HF) patients. Up to 30% of HF patients suffer from depression and even more have depressive symptoms. Moreover, depression carries a risk for HF, especially in high-risk groups, and is significantly associated with worse quality of life and clinical outcomes. The pathophysiology of depression and HF is poorly understood, but both diseases share several mechanisms and risk factors, including dysregulation of platelet reactivity, inflammation, neuroendocrine function, arrhythmias, high-risk behaviours, and social factors. Current HF guidelines advise to screen HF patients for depression and several screening questionnaires are available. Ultimately, the diagnosis of depression is based on DSM-5 criteria. Depression treatment consists of non-pharmacological and pharmacological therapies. Non-pharmacological therapies, such as exercise training and cognitive-behavioural therapy, have been shown to have beneficial effects on depressive symptoms. Selective serotonin reuptake inhibitors, the mainstay of antidepressant therapy, appear to be safe in HF but have not shown superiority over placebo in HF in short- and long-term randomized clinical trials. New therapies to treat depression are under investigation and may offer the opportunity to improve depression management in HF, including N-methyl-D-aspartate receptor antagonists, repetitive transcranial magnetic stimulation and omega-3 supplementation. New technologies may offer several advantages for the screening and diagnosis of depression but they remain to be tested in future research. In this review, we examine the intersection of depression and HF, summarize the epidemiology and pathophysiology, and discuss new opportunities to diagnose and treat HF patients with depression.

Importance Despite evidence that guideline-directed medical therapy (GDMT) improves outcomes in patients with heart failure (HF) and reduced ejection fraction, many patients are undertreated. The Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment (GUIDE-IT) trial tested whether a strategy of using target concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) to guide optimization of GDMT could improve outcomes. Objective To examine medical therapy for HF in GUIDE-IT and potential reasons why the intervention did not produce improvements in medical therapy. Design, Setting, and Participants GUIDE-IT, a randomized clinical trial performed at 45 sites in the United States and Canada, was conducted from January 16, 2013, to September 20, 2016. A total of 894 patients with HF and reduced ejection fraction (≤40%) were randomized to NT-proBNP-guided treatment with a goal to suppress NT-proBNP concentrations to less than 1000 pg/mL vs usual care. This secondary analysis examined the medical therapy titration and reasons why the intervention did not produce improvements in care and outcomes. Data were analyzed March 27 to June 28, 2019. Main Outcomes and Measures For each encounter, medication titrations were captured. A reason was requested if a modification was not made. A Cox proportional hazards regression model was used to assess the independent association of drug class with outcomes. Results Among the 838 patients available for analysis (566 men [67.5%]; median age, 62.0 years), 6223 visits occurred during 24 months. Adjustments of HF medication were made during 2847 of 5218 qualified visits (54.6%) (all usual care visits and all guided care visits with NT-proBNP level ≥1000 pg/mL) in 862 patients (96.4%). Most adjustments occurred within the first 6 months, primarily within the first 6 weeks. The most common reasons for not adjusting were "clinically stable" and "already at maximally tolerated therapy." Only 130 patients (15.5%) achieved optimal GDMT (≥50% of the target dose of β-blockers or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or any dose of mineralocorticoid antagonists) at 6 months, an increase from the baseline (79 of 891 [8.9%]) but not different by treatment arm. Higher doses of β-blockers were associated with reduced risk of the composite outcome of HF hospitalization and cardiovascular death (hazard ratio [HR], 0.98; 95% CI, 0.97-1.00; P = .008) and of all-cause death (HR, 0.97; 95% CI, 0.95-0.99; P = .01). Higher doses of angiotensin-converting enzyme inhibitors (HR, 0.84; 95% CI, 0.75-0.93; P < .001) and angiotensin receptor blockers (HR, 0.84; 95% CI, 0.71-0.99; P = .04) were associated with reduced risk of all-cause death. Increasing doses of mineralocorticoid antagonists did not appear to be associated with improved outcomes. Conclusions and Relevance Despite a protocol-driven approach, many patients in GUIDE-IT did not receive medication adjustments and did not achieve optimal GDMT, including those with known elevated NT-proBNP concentrations. These results suggest that opportunities exist to titrate medications for maximal benefit in HF. GUIDE-IT may have failed to achieve treatment benefit because of therapeutic inertia in clinical practice, or current GDMT goals may be unrealistic. Trial Registration ClinicalTrials.gov Identifier: NCT01685840.

Abstract Aims To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. Methods and results The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08–5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). Conclusions Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

BackgroundCurrent guidelines recommend multiple drugs titrated to maximally-tolerated dose as Guideline Directed Medical Therapy (GDMT) for chronic heart failure (HF). In clinical trials, background therapy at randomization is often stated as being "optimized" but objective criteria supporting such assertion are lacking. We propose a simple scoring system to define GDMT, set thresholds for optimal therapy, and standardize comparisons across HF clinical trials.MethodsWe evaluated current ACC/AHA/HFSA and ESC HF guidelines and the GDMT definition in 8 HF drug and device trials. We created a score based on strength of evidence, literature review, and data regarding dose effects. The score was tested in 10 hypothetical clinical scenarios based on likely drug combinations in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Trial.ResultsFigure 1 shows the proposed score. Of the 10 clinical scenarios based on COAPT, 3 patients were not optimized according to the proposed score. The score performed well in defining GDMT in most of these clinical scenarios.ConclusionWe propose a simple score for measuring GDMT, which validates well in clinical scenarios from a modern clinical trial. Utilizing this system will help establish a quality threshold for background therapy according to guideline recommendations, and provide standards for comparison across clinical trials. Further research should be conducted to determine whether the proposed score correlates with clinical outcomes. Current guidelines recommend multiple drugs titrated to maximally-tolerated dose as Guideline Directed Medical Therapy (GDMT) for chronic heart failure (HF). In clinical trials, background therapy at randomization is often stated as being "optimized" but objective criteria supporting such assertion are lacking. We propose a simple scoring system to define GDMT, set thresholds for optimal therapy, and standardize comparisons across HF clinical trials. We evaluated current ACC/AHA/HFSA and ESC HF guidelines and the GDMT definition in 8 HF drug and device trials. We created a score based on strength of evidence, literature review, and data regarding dose effects. The score was tested in 10 hypothetical clinical scenarios based on likely drug combinations in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Trial. Figure 1 shows the proposed score. Of the 10 clinical scenarios based on COAPT, 3 patients were not optimized according to the proposed score. The score performed well in defining GDMT in most of these clinical scenarios. We propose a simple score for measuring GDMT, which validates well in clinical scenarios from a modern clinical trial. Utilizing this system will help establish a quality threshold for background therapy according to guideline recommendations, and provide standards for comparison across clinical trials. Further research should be conducted to determine whether the proposed score correlates with clinical outcomes.