Protocolized Natriuresis-Guided Decongestion Improves Diuretic Response: The Multicenter ENACT-HF Study.

BACKGROUND: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload. METHODS: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms. RESULTS: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P=0.852). CONCLUSIONS: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.

Rationale and Design of the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure Study.

AIMS: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively. METHODS AND RESULTS: The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N-terminal pro-B-type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization. CONCLUSIONS: The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.

Outcomes with Ventricular Assist Device Therapy for Advanced Heart Failure in North Macedonia: First Annual Report

INTRODUCTION: Mechanical circulatory support by a continuous-flow ventricular assist device (VAD) improves survival and quality of life in selected patients with advanced heart failure. Developing countries have been struggling to construct a contemporary and effective health care system to manage advanced heart failure. This observation represents the first annual report on clinical outcomes with VAD for patients with advanced heart failure in the Republic of North Macedonia. METHODS: Data from all patients with VAD implantations between November 2018 and December 2019 were collected. The etiology of the heart failure was dilated cardiomyopathy in 4 patients (57%), ischemic cardiomyopathy in 2 (28%), and hypertrophic cardiomyopathy in 1 (14%). The primary outcome was survival; secondary outcomes included adverse events defined according to the Interagency Registry for Mechanically Assisted Circulatory Support. RESULTS: A total of 7 patients (85% males, median age 56 years) received a VAD; 5 of them received left VAD, and the remaining 2 received biventricular VAD. There were no deaths. Observed morbidity during a mean follow-up of 216 days included 3 bleeding events in 1 patient, 2 patients with superficial driveline infection, and 1 minor stroke and a pump thrombosis, which were treated with VAD exchange. Significant improvement in quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire and the Functional Independence Measure™ instrument, was seen with all patients. CONCLUSIONS: Our results demonstrate a successful initiation of the VAD program in the Republic of North Macedonia. Proper training of a dedicated HF team supports the reproducibility of this treatment in developing countries.

Special Conditions in Venous Thrombembolism - Case Series.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a preventable cause of in-hospital death, and one of the most prevalent vascular diseases. There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with VTE. Many clinically important subgroups (including the elderly, those with recent bleeding, renal insufficiency, disseminated malignancy or pregnant patients) have been under-represented in randomized clinical trials. We still need information from real life data (as example RIETE). The paper presents case series with VTE in special conditions, including cancer associated thrombosis, malignant homeopathies, as well in high risk population.

Cardiac autotransplantation and ex vivo surgical repair of giant left atrium: a case presentation.

BACKGROUND: Chronic Mitral Valve disease is strongly associated with Left atrial enlargement; the condition has a high mortality risk. Clinical manifestations include atrial fibrillation, pulmonary hypertension, thromboembolic events, and in cases of Giant Left Atrium (GLA) and a distorted cardiac silhouette. Full sternotomy, conventional open-heart surgery, reductive atrioplasty and atrioventricular valve repair are required to resolve symptoms. However, these procedures can be complicated due to the posterior location of the GLA and concomitant right lateral protrusion. Cardiac autotransplantation is superior under these conditions; it provides improved visual access to the posterior atrial wall and mitral valve, hence, facilitates corrective surgical procedures. We aimed to assess the clinical outcome of patients undergoing cardiac autotransplantation as the primary treatment modality to resolve GLA. Moreover, we evaluated the procedural safety profile and technical feasibility. CASE PRESENTATION: Four patients, mean EuroSCORE II of 23.7% ± 7.7%, presented with heart failure, atrial fibrillation, left atrial diameter > 6.5 cm and a severe distorted cardiac silhouette; X-ray showed prominent right lateral protrusion. We performed cardiac autotransplantation using continuous retrograde perfusion with warm blood supplemented with glucose followed by atrioplasty, atrial plication, valve annuloplasty and valve repair on the explanted beating heart. The surgical approach reduced the left atrial area, mean reduction was - 90.71 cm2 [CI95% -153.3 cm2 to - 28.8 cm2, p = 0.02], and normalized pulmonary arterial pressure, mean decrease - 11.25 mmHg [CI95% -15.23 mmHg to - 7.272 mmHg, p = 0.003]. 3 out of 4 patients experienced an uneventful postoperative course; 2 out of 4 patients experienced a transient return to sinus rhythm following surgery. One was operated on in 2017 and is still in good condition; two other patients survived for more than 10 years; Kaplan-Meier determined median survival is 10.5 years. CONCLUSIONS: Cardiac autotransplantation is an elegant surgical procedure that facilitates the surgical remodelling of Giant Left Atrium. Surgical repair on the ex vivo beating heart, under continuous warm blood perfusion, is a safe procedure applicable also to high-risk patients.

Endothelial Nitric Oxide Synthase T-786C Mutation, Prothrombin Gene Mutation (G-20210-A) and Protein S Deficiency Could Lead to Myocardial Infarction in a Very Young Male Adult.

INTRODUCTION: Myocardial infarction is a rare medical event in young people. The main reasons include congenital coronary abnormalities, coronary artery spasm, and coronary thrombosis due to hypercoagulable states (hereditary and acquired). AIM: We present a case of a young male adult with myocardial infarction caused by a combination of gene mutations and anticoagulation protein deficiency. CASE PRESENTATION: A 19 years old young man was admitted to our hospital complaining of chest pain during the last two weeks. The patient did not have any known cardiovascular risk factors, except a positive family anamnesis. Subacute inferior nonST segment myocardial infarction was diagnosed according to the patient's history, electrocardiographic and laboratory findings. Coronary angiography revealed suboclusive thrombus in the proximal, medial and distal part of the right coronary artery (TIMI 2). Percutaneous coronary intervention was performed. Anticoagulant and antiagregant therapy (heparin, acetilsalicilic acid and clopidogrel) according to protocol was started. The hospital stay was uneventful. Homozygous endothelial nitric oxid synthase (eNOS) T-786-C mutation, heterozygote prothrombin gene mutation (G-20210-A), and protein S deficiency were verified from the thrombophilia testing. Other trombophilic tests were normal. Three months after discharge from hospital another coronary angiography was performed. It revealed normal coronary arteries. Four years after the attack, the patient is free of symptoms and another cardiovascular event. CONCLUSION: Combination of genetic mutations and anticoagulation protein deficiency could be a reasonable cause for myocardial infarction in a very young male adult without any other cardiovascular risk factors.