Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19).

The SARS-CoV-2 virus spreading across the world has led to surges of COVID-19 illness, hospitalizations, and death. The complex and multifaceted pathophysiology of life-threatening COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis warrants early interventions to address all components of the devastating illness. In countries where therapeutic nihilism is prevalent, patients endure escalating symptoms and without early treatment can succumb to delayed in-hospital care and death. Prompt early initiation of sequenced multidrug therapy (SMDT) is a widely and currently available solution to stem the tide of hospitalizations and death. A multipronged therapeutic approach includes 1) adjuvant nutraceuticals, 2) combination intracellular anti-infective therapy, 3) inhaled/oral corticosteroids, 4) antiplatelet agents/anticoagulants, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of individual, novel oral therapies have not delivered tools for physicians to combat the pandemic in practice. No single therapeutic option thus far has been entirely effective and therefore a combination is required at this time. An urgent immediate pivot from single drug to SMDT regimens should be employed as a critical strategy to deal with the large numbers of acute COVID-19 patients with the aim of reducing the intensity and duration of symptoms and avoiding hospitalization and death.

The use of midodrine in patients with advanced heart failure.

In many patients, the treatment of heart failure (HF) cannot be optimized because of pre-existing or treatment-induced hypotension. Midodrine, a peripheral alpha1-adrenergic agonist may allow for up-titration of neurohormonal antagonist therapy leading to improved outcomes. Ten consecutive patients with HF due to systolic dysfunction and symptomatic hypotension interfering with optimal medical therapy were started on midodrine. After a 6-month follow-up, a higher percentage of patients were on optimal HF therapy (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker mg % of optimal dose 20% vs 57.5%; P<.001) (beta-blockers mg % optimal dose 37.5% vs 75%; P<.001) (spironolactone/eplerenone mg % 43.7% vs 95%; P<.001). This led to an improvement in left ventricular ejection fraction (baseline 24+/-9.4 vs 32.2+/-9.9; P<.001) and clinical outcomes, with a significant reduction in total hospital admissions (32 vs 12; P=.02) and total hospital days (150 vs 58; P=.02).

Right ventricular failure in patients with preserved ejection fraction and diastolic dysfunction: an underrecognized clinical entity.

It is well recognized that patients with severe left ventricular (LV) systolic dysfunction develop pulmonary venous hypertension or postcapillary pulmonary hypertension, which leads to an increase in pulmonary vascular resistance (PVR) and right ventricular (RV) systolic failure. It is often underrecognized, however, that patients with heart failure with preserved LV ejection fraction and diastolic dysfunction may also develop postcapillary pulmonary hypertension with elevated PVR leading to RV systolic failure. This form of biventricular failure is a result of diastolic failure on the left in patients with preserved LV ejection fraction and systolic failure on the right. At this time, there are no randomized trials or guidelines addressing the management of patients with diastolic heart failure with and without resultant RV failure. The authors review the pathophysiology, clinical presentation, and suggested treatment of this underrecognized clinical entity.

A comparison of nesiritide vs. epoprostenol in a patient with precapillary pulmonary hypertension due to scleroderma complicated by postcapillary pulmonary hypertension.

To the best of our knowledge, acute decompensated left-sided heart failure with preserved left ventricular ejection fraction in a patient with scleroderma has not been previously reported. We describe a patient with severe pulmonary hypertension due to limited scleroderma in whom nesiritide led to marked reductions in pulmonary arterial and capillary wedge pressure as well as resolution of symptoms and pulmonary edema. Subsequent epoprostenol use was associated with an increase in pulmonary capillary wedge pressure and a recurrence of pulmonary edema. Thus, nesiritide may be the preferred agent in scleroderma patients with severe pulmonary hypertension and preserved left ventricular systolic function since epoprostenol may lead to adverse hemodynamic effects.

In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE).

OBJECTIVES: We sought to compare the in-hospital mortality of patients with acute decompensated heart failure (ADHF) who were receiving parenteral treatment with one of four intravenous vasoactive medications. BACKGROUND: There are limited data regarding the effects of the choice of intravenous vasoactive medication on in-hospital mortality in patients hospitalized with ADHF. METHODS: This was a retrospective analysis of observational patient data from the Acute Decompensated Heart Failure National Registry (ADHERE), a multicenter registry designed to prospectively collect data on each episode of hospitalization for ADHF and its clinical outcomes. Data from the first 65,180 patient episodes (October 2001 to July 2003) were included in this analysis. Cases in which patients received nitroglycerin, nesiritide, milrinone, or dobutamine were identified and reviewed (n = 15,230). Risk factor and propensity score-adjusted odds ratios (ORs) for in-hospital mortality were calculated. RESULTS: Patients who received intravenous nitroglycerin or nesiritide had lower in-hospital mortality than those treated with dobutamine or milrinone. The risk factor and propensity score-adjusted ORs for nitroglycerin were 0.69 (95% confidence interval [CI] 0.53 to 0.89, p < or = 0.005) and 0.46 (94% CI 0.37 to 0.57, p < or = 0.005) compared with milrinone and dobutamine, respectively. The corresponding values for nesiritide compared with milrinone and dobutamine were 0.59 (95% CI 0.48 to 0.73, p < or = 0.005) and 0.47 (95% CI 0.39 to 0.56, p < or = 0.005), respectively. The adjusted OR for nesiritide compared with nitroglycerin was 0.94 (95% CI 0.77 to 1.16, p = 0.58). CONCLUSIONS: Therapy with either a natriuretic peptide or vasodilator was associated with significantly lower in-hospital mortality than positive inotropic therapy in patients hospitalized with ADHF. The risk of in-hospital mortality was similar for nesiritide and nitroglycerin.

Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE).

BACKGROUND: The ADHERE is designed to study characteristics, management, and outcomes in a broad sample of patients hospitalized with acute decompensated heart failure. Heart failure is a leading cause of hospitalization for adults older than 65 years in the United States. Most available data on these patients are limited by patient selection criteria and study design of clinical trials and single-center studies. METHODS: Participating hospitals identify patients with a primary or secondary discharge diagnosis of heart failure. Medical history, management, treatments, and health outcomes data are collected through review of medical records and entered into a database via secure web browser technology. RESULTS: As of January 2004, data on 107 362 patients have been received from 282 participating hospitals. Of enrollees with available analyzable data (N = 105 388 from 274 hospitals), the mean age was 72.4 (+/-14.0), and 52% were women. The most common comorbid conditions were hypertension (73%), coronary artery disease (57%), and diabetes (44%). Evidence of mild or no impairment of systolic function was found in 46% of patients. Inhospital mortality was 4.0% and the median hospital length of stay was 4.3 days. CONCLUSIONS: The ADHERE demonstrates both the feasibility and significant implications of gathering representative data on large numbers of patients hospitalized with heart failure. Initial data provided important insights into the clinical characteristics and patterns of care of these patients. Ongoing registry work will provide the framework for improved treatment strategies for patients hospitalized with decompensated heart failure.

Safety and feasibility of using serial infusions of nesiritide for heart failure in an outpatient setting (from the FUSION I trial).

The Follow-Up Serial Infusions of Nesiritide pilot study was designed to assess the safety and tolerability of outpatient serial infusions of nesiritide in 210 patients with decompensated heart failure who were randomly assigned to usual care only or usual care plus weekly infusions of nesiritide at dosages of 0.005 or 0.01 microg/kg/min for 12 weeks. The mean age +/- SD of the entire population was 67 +/- 13 years; 70% were men, and 80% were white. Mean baseline serum creatinine levels were 1.8 +/- 0.7 mg/dl, and mean left ventricular ejection fraction was 0.28 +/- 0.15%. Diabetes mellitus was present in 106 patients (50%), and atrial arrhythmias were present in 100 patients (48%). A totalof 1,645 nesiritide infusions was administered; 11 (< 1%) were discontinued due to an adverse event. All treatment groups had a similar frequency of adverse events and experienced improvements in quality of life. Administration of nesiritide resulted in acute decreases in aldosterone and endothelin-1 concentrations. Although there were no statistically significant differences among groups by outcome, prospectively defined higher risk subgroups demonstrated significant decreases in cardiovascular events. These results demonstrate the safety and feasibility of administering nesiritide in an outpatient setting. Additional studies are needed to determine the effect of outpatient serial infusions of nesiritide on rates of morbidity and mortality in advanced heart failure.