Intrarenal Venous Doppler as a novel marker for optimal decongestion, patient management, and prognosis in Acute Decompensated Heart Failure.

AIMS: An increase in right atrial pressure is a common feature of acute decompensated heart failure (ADHF). Such increased pressure leads to persistent kidney congestion. A marker to guide optimal diuretic therapy is missing. We aim to correlate intrarenal Doppler (IRD) ultrasound in ADHF patients with clinical outcomes to assess whether renal haemodynamic parameter changes are useful for monitoring kidney congestion. METHODS AND RESULTS: Between December 2018 and January 2020, ADHF patients requiring intravenous diuretic therapy for at least 48 h were considered for study selection. An IRD blinded examination was performed on Days 1, 3, and 5, and clinical and laboratory parameters were recorded. Venous Doppler profiles (VDP) were classified as continuous (C), pulsatile (P), biphasic (B), or monophasic (M) according to the congestion degree; B and M profiles were considered deranged. A VDP improvement (VDPimp) was defined as a change of ≥1 pattern degree or maintenance of C or P patterns. An arterial resistive index (RI) > 0.8 was considered elevated. Outcomes of death and rehospitalization were gathered at 60 days. Data were assessed by regression and Kaplan-Meier analyses. All 177 ADHF patients admitted were screened, and 72 were enrolled [27 females-median age 81 (76-87) years-median ejection fraction 40% (30-52)]. The VDP derangement decreased from 79.2% on Day 1 to 51.4% on Day 5 (P < 0.05). The RI elevation decreased from 60.6% on Day 1 to 43.1% on Day 5 (P < 0.05). At Day 5, VDPimp was registered in over half of the patients (59.7%). At Day 5, signs of congestion (dyspnoea/oedema/rales), fluid accumulation (pleural/peritoneal fluid), haematocrit, and brain natriuretic peptide improved (P > 0.05). After 60 days, 12 (16.7%) patients were readmitted and 9 (12.5%) died. The VDPimp was identified as the unique independent factor associated with readmission [Hazard Ratio (HR) 0.22, 95% (confidence interval) CI 0.05-0.94, P = 0.04] and death (HR 0.07, 95% CI 0.01-0.68, P = 0.02), with significantly better outcomes identified in VDPimp patients (log-rank test, P < 0.05). CONCLUSION: Decongestion may be associated with improvements in many clinical and instrumental parameters, but only VDPimp was associated with better clinical outcomes. The VDPimp should be incorporated in ad hoc ADHF clinical trials to better define its role in everyday practice.

Effects of Cholecalciferol Supplementation in Patients with stable heart failure and LOw vITamin D levels (ECSPLOIT-D): a double-blind, randomized, placebo-controlled pilot study.

BACKGROUND: The aim of this study was to investigate the effects of vitamin D (VD) on the interaction among functional, echocardiographic and hormonal parameters in patients with heart failure (HF) and VD deficiency. METHODS: In a randomized, double blind trial, 35 patients with HF and VD<20 ng/mL, received either 300,000 U of oral cholecalciferol followed by 50,000 U/month for 6 months, or placebo treatment. RESULTS: Changes in the 6 Minute Walking Test (6MWT) assessed at 3 and 6 months in treatment group was the primary end point. Secondary endpoints were echocardiographic and hormonal changes. The same targets were compared in treated and placebo groups as secondary endpoints. In the treatment group the 6MWT improved at 3 (from 210±104 mt to 225±94 mt; P=0.033) but not at 6 months (from 210±104 mt to 217±94 mt; P=0.288) while PTH dropped at 3 (from 76.8±50.5 to 50.2±20.3 pg/mL; P=0.025), but not at 6 months. 6MWT improvement was negatively related to baseline VD levels. Variation in 6MWT did not significantly differ among groups at 3 (13.6±23.3 vs. 3.6±17.3; P 0.175) and 6 months (12.1±31.4 vs. 0.2±23.2; P 0.225). Left atrial size increased in the placebo group (from 50.8±20.7 to 61.7±36.0 mL/m2; P=0.010). Other hormonal parameters remained unchanged. CONCLUSIONS: In summary, the treatment of VD deficiency in patients with HF improved 6MWT after 3 months along with a decrease in PTH levels. However when compared with the placebo arm, treatment of VD deficiency did not influence the final outcomes.

Does coronary Atherosclerosis Deserve to be Diagnosed earlY in Diabetic patients? The DADDY-D trial. Screening diabetic patients for unknown coronary disease.

OBJECTIVES: To evaluate if screening and treatment of asymptomatic coronary artery disease (CAD) are effective in preventing first cardiac event in diabetics. METHODS: Diabetic patients without known CAD were randomly assigned to undergo a screening for silent myocardial ischemia followed by revascularization or to continue follow-up. The reduction of cardiac death (CD) or nonfatal myocardial infarction (MI) represented the primary aim; secondary aim was the prevention of heart failure (HF). RESULTS: From September 2007 to May 2012, 520 patients (62 years; 104 female) were enrolled. Silent CAD was found in 20 of 262 patients (7.6%), revascularization was performed in 12 (4.6%). After a mean follow-up of 3.6 years 12 events (4.6%) occurred in the study group and 14 (5.4%) in the follow-up (HR=0.849, 95% CI: 0.393-1.827, P=0.678). The occurrence of first HF episode did not differ between groups: 2 (0.8%) in screened and 7 (2.7%) in follow-up (HR=0.273, 95% CI: 0.057-1.314, P=0.083). Subgroup analysis revealed a significantly lower HF episodes among patients with intermediate cardiovascular risk (Log rank P=0.022). Additionally, when CD and MI were analysed within subgroups, a significant lower number of CDs was observed among older than 60 years (P=0.044). CONCLUSION: Screening and revascularization of silent CAD in diabetics, failed to demonstrate a significant reduction in cardiac events and HF episodes. However, our data indicate that further research is warranted in patients older than 60 years and those with an intermediate cardiovascular risk. CLINICALTRIALS.GOV: NCT00547872.

Screening asymptomatic patients with diabetes for unknown coronary artery disease: does it reduce risk? An open-label randomized trial comparing a strategy based on exercise testing aimed at revascularization with management based on pharmacological/behavioural treatment of traditional risk factors. DADDY-D Trial (Does coronary Atherosclerosis Deserve to be Diagnosed and treated early in Diabetics?).

BACKGROUND: Coronary artery disease is the leading cause of morbidity and mortality in patients with type 2 diabetes. Screening for asymptomatic coronary artery disease with treatment by means of revascularization seems to be an appealing option for prevention. The utility of such a strategy has never been challenged in a randomized trial. METHODS/DESIGN: In the present study a cohort of diabetic patients without any symptoms and without known coronary artery disease will be screened at two diabetes outpatients services. Those with intermediate or high risk (equal or greater than 10% according to the Italian risk chart) will be asked to participate and enrolled. They will be seen and followed in order to provide the best adherence to medical therapy. Half of the patients will be randomized to undergo an exercise tolerance testing while the other group will continue to be regularly seen at diabetes outpatients services. Best medical/behavioral therapy will be offered to both groups. Those patients with a positive exercise tolerance testing will be studied by coronary angiography and treated according to the severity of coronary lesions by percutaneous stenting or surgery.The objective of the study is to evaluate the efficacy of the screening strategy aimed at revascularization. A cost-effectiveness analysis will be performed at the end of the follow up. DISCUSSION: The study will provide useful information about prevention and treatment of diabetic patients at high risk of coronary events. It will be made clearer if detection of silent coronary artery disease has to be recommended and followed by treatment. Given the simplicity of the study protocol, it will be easily transferable to the real world. TRIAL REGISTRATION: (ClinicalTrials.gov): NCT00547872.