Development and validation of SCOPE score: A clinical score to predict COVID-19 pneumonia progression to severe respiratory failure.

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

Loop diuretics for chronic heart failure: a foe in disguise of a friend?

Loop diuretics are recommended for relieving symptoms and signs of congestion in patients with chronic heart failure and are administered to more than 80% of them. However, several of their effects have not systematically been studied. Numerous cohort and four interventional studies have addressed the effect of diuretics on renal function; apart from one prospective study, which showed that diuretics withdrawal is accompanied by increase in some markers of early-detected renal injury, all others converge to the conclusion that diuretics receipt, especially in high doses is associated with increased rates of renal dysfunction. Although a long standing perception has attributed a beneficial effect to diuretics in the setting of chronic heart failure, many cohort studies support that their use, especially in high doses is associated with adverse outcome. Several studies have used propensity scores in order to match diuretic and non-diuretic receiving patients; their results reinforce the notion that diuretics use and high diuretics dose are true risk factors and not disease severity markers, as some have suggested. One small, randomized study has demonstrated that diuretics decrease is feasible and safe and accompanied by a better prognosis. In conclusion, until elegantly designed, randomized trials, powered for clinical endpoints answer the unsettled issues in the field, the use of diuretics in chronic heart failure will remain subject to physicians' preferences and biases and not evidence based.

Arteriovenous renal replacement therapy in end-stage left-sided heart failure patients has a detrimental effect on patients with impaired right ventricular function.

OBJECTIVE: Chronic intermittent renal replacement therapy(RRT) is an alternate method of decongestion for patients presenting with diuretic-resistant, end-stage heart failure(HF) and cardiorenal syndrome. The optimal method of vascular access has not been confirmed. This study investigated the 6-month outcomes of patients with end-stage HF after the creation of arteriovenous communications (AVC) compared with other means of RRT. METHODS: We treated 40 patients with chronic, intermittent, ambulatory RRT, of whom 15 (37.5%; Group A) underwent creation of AVC, and 25 (62.5%; Group B) received intraperitoneal (n=6) or internal jugular catheters (n=19) with the goal of achieving body weight stabilization and relief from congestion. RESULTS: The characteristics of the two groups were similar. According to Cox regression analysis, the 6-month rate of death or re-hospitalization for HF was significantly higher in Group A (73%) than in Group B (44%); hazard ratio (HR): 2.58; 95% confidence interval (CI) 1.2-6.2; P=0.02. Over a 6-month follow-up, the cumulative survival was significantly shorter (P=0.03) in Group A (13.8±10 weeks) than in Group B (20.7±7 weeks). In the 15 patients who received AVC, the only independent predictor of adverse outcome at 6 months was serum total bilirubin concentration (HR 2.5; 95% CI 1.1-5.7, p=0.02), whereas in the 25 patients who underwent other means of RRT, pulmonary vascular resistance (PVR) was identified as a risk factor for hospitalization or death at 1-year follow-up (HR 1.26; 95% CI 1.1-1.57, p=0.04). CONCLUSION: In patients with end-stage HF, the creation of AVC for intermittent RRT was followed by a significant increase in morbidity and mortality in comparison to the safe and effective placement of permanent central venous catheters. Patients with elevated PVR seem to comprise a group at high risk for adverse outcomes after central catheter insertion.

Long-Term Intra-Aortic Balloon Pump Support as Bridge to Left Ventricular Assist Device Implantation.

BACKGROUND: The intra-aortic balloon pump (IABP) can be used to bridge critically ill end-stage heart failure patients to left ventricular assist device (LVAD) implantation. However, the IABP's potential association with hemorrhagic complications raises concerns regarding its utilization in these patients. AIM: We investigated whether preoperative long-term IABP support increases hemorrhagic complications post-LVAD implantation. METHODS: Ten patients undergoing IABP support prior to LVAD implantation (IABP-LVAD group) were compared with 16 who did not require IABP support (LVAD group). RESULTS: Mean duration of IABP support was 25.8 days. Preoperatively, both groups were comparable in all measured parameters and indices of end-organ function. Perioperative (defined as three weeks post-LVAD implantation, including the procedure) cellular and noncellular blood transfusion requirements were similar between IABP-LVAD and LVAD groups (19.8 ± 9.95 vs. 19.76 ± 29.69 RBC units, p = 0.96; 3.8 ± 4.14 vs. 2.0 ± 6.44 plateletpheresis units p = 0.84; 23 ± 16.04 vs. 25.14 ± 37.8 fresh frozen plasma units, p = 0.45). Perioperative minimum hematocrit (33.6 ± 5.6 vs. 36.59 ± 4.8, p = 0.38) and minimum platelet count (199 ± 153 vs. 144 ± 65, p = 0.52) were similar in the two groups. Two patients in the IABP-LVAD group and three patients in the LVAD group underwent reoperation post-LVAD implantation for bleeding. Length of ICU stay was longer in the LVAD group but did not reach statistical significance (6.2 ± 6.22 days in the IABP-LVAD group versus 13.45 ± 10.95 days in the LVAD group, p = 0.06). CONCLUSIONS: Long-term IABP support as a bridge to LVAD implantation is not associated with increased hemorrhagic complications post-LVAD implantation. doi: 10.1111/jocs.12759 (J Card Surg 2016;31:467-471).

Attenuated Microcirculatory Response to Maximal Exercise in Patients With Chronic Heart Failure.

PURPOSE: Exercise training programs improve microcirculatory alternations in patients with chronic heart failure (CHF). However less is known about the acute effect of maximum exercise on the skeletal muscle microcirculation. We aimed to assess the effect of acute exercise on peripheral microcirculation of patients with CHF, as assessed by near-infrared spectroscopy with vascular occlusion technique. METHODS: Tissue oxygenation was evaluated in 8 stable patients with CHF (7 males; mean age, 60 ± 9 years; body mass index, 26.3 ± 3.8 kg/m) and 8 healthy subjects (matched for age, sex, and body mass index) before and after cardiopulmonary exercise testing. Tissue oxygen saturation (StO2), StO2peak, oxygen consumption rate, and endothelial function (reperfusion rate), before and after maximum exercise, were assessed. RESULTS: Patients with CHF had lower StO2 and reperfusion rate compared with healthy subjects (71.4% ± 9.8% vs 81.0% ± 5.4% and 9 ± 1 %/min vs 13.9 ± 5.8%/min, respectively; P < .05) at rest. Oxygen consumption rate increased after exercise in patients with CHF and healthy subjects (from -31.7 ± 8.2 to -43.7 ± 12.7 and from -35.7 ± 6.7 to -42.4 ± 6.4, respectively; P < .05). StO2 decreased significantly after maximal exercise in patients with CHF (from 71.4 ± 9.8 to 65.2 ± 12.7; P < .05), whereas it returned to the preexercise values in healthy subjects (from 81.0 ± 5.4 to 80.3 ± 7.0). There was a significant between-group difference (P < .05). CONCLUSIONS: Patients with CHF present microcirculatory alternations. Acute exercise exerts an effect on microcirculation in peripheral, nonexercising muscles, with altered response in patients with CHF compared with healthy subjects.

Late-onset right ventricular dysfunction after mechanical support by a continuous-flow left ventricular assist device.

BACKGROUND: Right heart failure (RHF) is a serious post-operative complication of left ventricular assist device (LVAD) implantation, with significant morbidity and mortality. Many clinical, hemodynamic and laboratory variables have been shown to have prognostic value for appearance of RHF. We sought to investigate the incidence of new-onset right ventricular dysfunction (RVD) complicating the long-term use of LVADs. METHODS: We retrospectively examined all patients supported with a continuous-flow LVAD for >1 year at our center. RESULTS: Twenty patients (mean age 54 ± 10 years, 95% men, 60% with ischemic cardiomyopathy, left ventricular ejection fraction 22 ± 6%, pulmonary capillary wedge pressure 23.5 ± 7.5 mm Hg, brain natriuretic peptide [BNP] 1,566 ± 1,536 pg/ml, serum creatinine 1.6 ± 0.64 mg/dl, furosemide dose 643 ± 410 mg/day) underwent long-term mechanical support as destination therapy support with a continuous-flow LVAD (HeartMate II) at our center. During follow-up (1,219 ± 692 days), 9 patients (45%) manifested symptoms and signs of RVD (increase in right atrial pressure [RAP], BNP and daily furosemide dose compared with the early post-operative period). In these patients, RAP was increased by 6.6 ± 2.6 mm Hg and BNP by 526 ± 477 pg/ml, whereas furosemide dose increased by 145 ± 119 mg. The mean and median times of RVD onset were 2.3 ± 1.5 and 2.1 years, respectively, after LVAD implantation (range 0.4 to 4.8 years). Four of these patients (44.4%) demonstrated further deterioration of RV function and died 73 ± 106 days (median 25 days, range 9 to 231 days) after first manifestation of RVD. Comparisons of baseline variables regarding medical history and clinical status did not demonstrate significant differences between the patients with or without RVD, including parameters related to RV function at the time of implantation. CONCLUSIONS: Late-onset RVD is a complication of LVAD support, which can manifest several months to years from device implantation. This complication has significant adverse implications with regard to patient outcome. Prognostic factors need to be identified to follow and treat high-risk patients more efficiently.

Prolonged intra-aortic balloon pump support in biventricular heart failure induces right ventricular reverse remodeling.

BACKGROUND: Right ventricular dysfunction is associated with high morbidity and mortality in candidates for left ventricular assist device (LVAD) implantation or cardiac transplantation. METHODS: We examined the effects of prolonged intra-aortic balloon pump (IABP) support on right ventricular, renal and hepatic functions in patients presenting with end-stage heart failure. RESULTS: Between March 2008 and June 2013, fifteen patients (mean age = 49.5 years; 14 men) with end-stage systolic heart failure (HF), contraindications for any life saving procedure (conventional cardiac surgery, heart transplantation, LVAD implantation) and right ventricular dysfunction were supported with the IABP. The patients remained on IABP support for a mean of 73 ± 50 days (median 72, range of 13-155). We measured the echocardiographic and hemodynamic changes in right ventricular function, and the changes in serum creatinine and bilirubin concentrations before and during IABP support. Mean right atrial pressure decreased from 12.7 ± 6.5 to 3.8 ± 3.3 (P < 0.001) and pulmonary artery pressure decreased from 35.7 ± 10.6 to 25 ± 8.4 mmHg (P = 0.001), while cardiac index increased from 1.5 ± 0.4 to 2.2 ± 0.7 l/m(2)/min (P = 0.003) and right ventricular stroke work index from 485 ± 228 to 688 ± 237 mmHg × ml/m(2) (P = 0.043). Right ventricular end-diastolic diameter decreased from 34.0 ± 6.5 mm to 27.8 ± 6.2 mm (P < 0.001) and tricuspid annular systolic tissue Doppler velocity increased from 9.6 ± 2.4 cm/s to 11.1 ± 2.3 cm/s (P = 0.029). Serum creatinine and bilirubin decreased from 2.1 ± 1.3 to 1.4 ± 0.6 mg/dl and 2.0 ± 1.0 to 0.9 ± 0.5 mg/dl, respectively (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: Prolonged IABP support of patients presenting with end-stage heart failure and right ventricular dysfunction induced significant improvement in right ventricular and peripheral organ function.

High furosemide dose has detrimental effects on survival of patients with stable heart failure.

INTRODUCTION: High doses of furosemide for heart failure (HF) have been correlated with an increased mortality, though whether they are a marker of disease severity or an independent predictor is unknown. We hypothesized that, in patients presenting with stable HF, the likelihood of long-term major adverse clinical events is increased by higher furosemide doses. METHODS: We retrospectively recorded the doses of furosemide prescribed to 173 consecutive, clinically stable patients during a first ambulatory HF department visit. The low-dose group included 103 patients treated with 80 mg and the high-dose group included 70 patients treated with >80 mg of furosemide daily. Proportional hazard regression analyses were performed with single and multiple variables in search of correlates of long-term adverse clinical events. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. RESULTS: The baseline characteristics of the 2 groups were similar, except for estimated glomerular filtration rate, which was higher in the low- than the high-dose group (72.9 ± 19.4 vs. 60.8 ± 22.0 mL/min/ m2, p<0.001). The 3-year survival free from the composite endpoint was significantly higher in the lowdose group than in the high-dose group (93.1% vs. 60.0%, p<0.001). By multiple variable analysis, highdose furosemide was an independent predictor of an adverse outcome at 3 years (adjusted HR: 15.25; 95% CI:1.06-219.39, p=0.045). The incidence of deterioration of renal function and episodes of hypokalemia during follow up was also higher in the high furosemide dose (73.2% vs. 48.3, p=0.003, and 43.1% vs. 6.5%, p<0.001, respectively). CONCLUSIONS: High doses of furosemide administered in order to stabilize HF patients and continued thereafter are associated with an adverse clinical outcome.

Dabigatran etexilate as second-line therapy in patients with a left ventricular assist device.

INTRODUCTION: Administration of anticoagulation is mandatory in patients with left ventricular assist devices (LVADs). Vitamin K antagonists require regular monitoring and dosage adjustment. Dabigatran administered in a standard dose twice daily is more convenient and achieves a stable anticoagulant effect, but its effectiveness and safety in patients with LVADs has not been investigated. The objective of the present study was to evaluate whether dabigatran can be used safely as a second-line anticoagulation option in patients with a HeartMate II (HMII) LVAD. METHODS: The study population consisted of 7 consecutive patients with end-stage heart failure who underwent HMII implantation and sequentially received acenocoumarol and dabigatran. Occurrence of stroke, systematic embolism, device thrombosis and major or life-threatening bleeding were included in the analysis. An acute decrease in plasma hemoglobin >2 g/dL or a need for transfusion of at least 2 units of packed red blood cells (PRBC) was defined as major bleeding, while an acute decrease in plasma hemoglobin >5 g/dL, fatal, symptomatic intracranial bleed, need for transfusion of at least 4 units PRBC, or association with hypotension requiring the use of intravenous inotropic agents or surgical intervention was defined as life-threatening bleeding. RESULTS: The duration of follow up was 1564 ± 292 days. Patients received acenocoumarol for 855 ± 246 days, followed by dabigatran for 708 ± 368 days. The rates of thromboembolic events were similar under dabigatran and acenocoumarol treatment: strokes, 0.094 vs. 0 /patient-year, p=0.36; systemic embolism, no event in either group; and device thrombosis, 0.053 vs. 0.258 events/patient-year, p=0.19, respectively. Compared to an adjusted acenocoumarol dose, the standard dabigatran dose resulted in similar rates of life-threatening bleeding, but significantly lower rates of major bleeding (0.18 vs. 0.27 bleeds/patient-years, p=0.76, and 0.047 vs. 0.547, p<0.001, for dabigatran and acenocoumarol, respectively). CONCLUSIONS: The safe and effective use of dabigatran as a second-line anticoagulation therapy in patients with HMII seems feasible. However, these data must be confirmed in a randomized study.

Outpatient management of chronic heart failure.

INTRODUCTION: Heart failure (HF) treatment attracts a share of intensive research because of its poor HF prognosis. In the past decades, the prognosis of HF has improved considerably, mainly as a consequence of the progress that has been made in the pharmacological management of HF. AREAS COVERED: This article reviews the outpatient pharmacological management of chronic HF due to left ventricular systolic dysfunction and offers recommendations on the use of various drugs. In addition, the present article attempts to provide practical therapeutic algorithms based on current clinical strategies. EXPERT OPINION: Continued research directed toward identifying factors associated with high pharmacotherapy guideline adherence and understanding of variants that influence response to drugs will hopefully halt or reverse the major pathophysiological mechanisms involved in this syndrome.

Red blood cell distribution width is a significant prognostic marker in advanced heart failure, independent of hemoglobin levels.

INTRODUCTION: Advanced heart failure (HF) is associated with increased morbidity and mortality; traditionally used prognostic factors often fail to predict the outcome. Increased red blood cell distribution width (RDW) has recently been recognized as an important unfavorable prognostic factor in HF, independent of anemia; however, the role of RDW in patients with advanced HF has not yet been investigated. METHODS: Eighty consecutive patients with stage D heart failure, recently hospitalized for HF decompensation, were enrolled. A Cox proportional-hazard model was used to determine whether RDW was independently associated with outcome. RESULTS: At study entry, ejection fraction (EF), pulmonary capillary wedge pressure (PCWP), hemoglobin (Hb) and RDW were 25 ± 8.6%, 27.5 ± 8 mmHg, 12.5 ± 1.9 mg/dL and 18 ± 3.5% (normal <14.5%) respectively. At 6 months, 44 patients (55%) had died. In this patient population, EF (p=0.45), PCWP (p=0.106), age (p=0.54), albumin (0.678), iron (p=0.37), creatinine (p=0.432), iron deficiency defined by bone marrow aspiration (p=0.37), bilirubin (p=0.422), peak VO2 (p=0.057) and Hb (p=0.95) were not significant predictors of a worse outcome. However, RDW was a significant marker for adverse prognosis (p=0.007, HR: 1.14, CI: 1.04-1.24) and retained its prognostic significance even when corrected for Hb values (HR: 1.15, CI: 1.05-1.27, p=0.003). CONCLUSIONS: RDW is a significant prognostic factor for an adverse outcome in patients with advanced stage heart failure who have experienced recent decompensation, independent of the presence of anemia or malnutrition, and is superior to more traditionally used indices. RDW may be associated with severe disease by reflecting subtle metabolic and proinflammatory abnormalities in HF.

Elevated left ventricular filling pressures can be estimated with accuracy by a new mathematical model.

BACKGROUND: Although the clinical assessment of jugular venous pressure (JVP) provides accurate estimate of right atrial pressure (RAP), there is no reliable non-invasive method for assessing pulmonary capillary wedge pressure (PCWP). Our objective was to evaluate the sensitivity and specificity for detecting elevated left ventricular filling pressures using a model for PCWP estimation, based on the clinical assessment of RAP and association between RAP and PCWP, which is unique for each patient, identified in a recent right heart catheterization (RHC). METHODS: The study included 377 patients (age, 54.3 ± 13 years) with heart failure with reduced ejection fraction (left ventricular ejection fraction of 30.5 ± 10.8%) who underwent 2 RHCs within 1 year. In Group A (189 randomly selected patients), hemodynamic variables with significant correlation with the current wedge pressure (PCWP(2)) were identified and an equation estimating PCWP(2) based on these variables was formed. The validity of the equation was evaluated in the remaining 188 patients (Group B). The equation was also evaluated, prospectively in 39 new patients where RAP was estimated clinically, by physicians blinded to the results of the RHC. RESULTS: PCWP(2) in Group A correlated with RAP(1), systolic pulmonary artery pressure (SPAP(1)), and PCWP(1) of the first RHC and with RAP(2) and SPAP(2) of the second. The equation is PCWP(2) = [3RAP(2) + (PCWP(1) - RAP(1)) + 4]/2. In Group B, the sensitivity and specificity of estimated PCWP(2) for diagnosis of elevated LV filling pressures (invasive values >18 mm Hg) was significant, reflected by an area under the curve (AUC) of 0.954 (p < 0.001). In the prospective sub-group, where JVP was entered in the formula as an estimate of RAP(2), correlation between estimated and measured PCWP(2) was r = 0.803 (p < 0.001). CONCLUSIONS: The current PCWP of a patient with heart failure can be estimated accurately by a simple equation based on measurements of a previous RHC and the current value of clinically assessed JVP.

Amiodarone attenuates the proarrhythmic effects of dobutamine in patients with advanced congestive heart failure.

INTRODUCTION: The long-term use of positive inotropic pharmaceuticals in patients suffering from end-stage congestive heart failure (CHF) has been associated with increased mortality, presumed to be due to proarrhythmia. Oral amiodarone combined with intermittent dobutamine infusions (IDI), on the other hand, has been shown to increase survival. This study evaluated the effects of oral amiodarone on the arrhythmias caused by dobutamine in patients with advanced CHF. METHODS: Thirty patients with CHF, in New York Heart Association functional class III or IV despite optimal medical therapy, were treated with weekly 8-h infusions of dobutamine 10 Ig/kg/min. All patients were treated for 1 month with oral amiodarone, 400 mg/day, before initiation of IDI. A 24-h ambulatory electrocardiogram was recorded on the day before dobutamine infusion and repeated the next day, starting with the onset of infusion. RESULTS: The average heart rate on the 24-h ambulatory electrocardiogram was 72 +/- 14 beats/min before vs. 72 +/- 12 beats/min during IDI (p=1.000). Likewise, dobutamine did not increase the frequency of premature ventricular complexes (23 +/- 32 per h before vs. 42 +/- 69 per h during infusion, p=0.131), ventricular couplets (18 +/- 36 per 24 h vs. 17 +/- 28 per 24 h, p=0.859), or the incidence of non-sustained ventricular tachycardia (27% vs. 40%, p=0.383). No patient developed ventricular fibrillation or sustained ventricular tachycardia during or after IDI. CONCLUSIONS: Chronic low-dose oral amiodarone attenuates the proarrhythmic effects of dobutamine, increasing the safety of ambulatory IDI.

Intermittent inotropic infusions combined with prophylactic oral amiodarone for patients with decompensated end-stage heart failure.

BACKGROUND: Concern has been raised regarding the mortality and ethics related to the treatment of patients with end-stage chronic heart failure with chronic intermittent intravenous inotropic agents. We examined whether intermittent inotropic agents combined with oral amiodarone to prevent the proarrhythmic effect of inotropic agents results in better outcomes. METHODS: The study included 162 patients with decompensated end-stage chronic heart failure, who could be weaned from an initial 72-hour infusion of intravenous inotropes. Group 1 included 140 patients, who entered a 6-month program of weekly intermittent intravenous inotropic agents plus oral amiodarone, 200 mg twice a day. Group 2 included 22 patients, who were treated with optimal conventional therapy and were hospitalized for administration of intravenous medications as needed. RESULTS: The baseline characteristics of groups 1 versus 2, including New York Heart Association functional class (IV in both groups), admission systolic arterial blood pressure (99 +/- 14 vs. 97 +/- 13 mm Hg), right atrial pressure (13 +/- 6 vs. 14 +/- 6 mm Hg), pulmonary capillary wedge pressure (28 +/- 7 vs. 31 +/- 10 mm Hg), serum sodium (136 +/- 7 vs. 139 +/- 6 mEq/L) and serum creatinine (1.7 +/- 0.8 vs. 1.8 +/- 1.8 mg/dL), were similar. The 6-month (51% vs. 18%) and 1-year (36% vs. 9%) survival rates were significantly higher (P = 0.001 for both) in group 1 than in group 2. In addition, patients treated with intermittent intravenous inotropic agents improved their functional and hemodynamic status. CONCLUSIONS: Intermittent intravenous inotropic agents combined with prophylactic oral amiodarone seem to improve the outcomes of patients with end-stage chronic heart failure. Further research is warranted to elucidate whether this treatment strategy should be considered as a standard therapy in patients with refractory end-stage heart failure.