Guideline-based audit of the hospital management of heart failure with reduced ejection fraction.

BACKGROUND: Heart failure is a major burden in Australia in terms of morbidity, mortality and healthcare expenditure. Multiple evidence-based therapies are recommended for heart failure with reduced ejection fraction (HFrEF), but data on physician adherence to therapy guidelines are limited. AIM: To compare use of HFrEF therapies against current evidence-based guidelines in an Australian hospital inpatient population. METHODS: A retrospective review of patients admitted with a principal diagnosis of HFrEF across six metropolitan hospitals in Sydney, Australia, between January 2015 and June 2016. Use of medical and device therapies was compared with guideline recommendations using individual patient indications/contraindications. Readmission and mortality data were collected for a 1-year period following the admission. RESULTS: Of the 1028 HFrEF patients identified, 39 were being managed with palliative intent, leaving 989 patients for the primary analysis. Use of beta-blockers (87.7% actual use/93.6% recommended use) and diuretics (88.4%/99.3%) was high among eligible patients. There were large evidence-practice gaps for angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB; 66.4%/89.0%) and aldosterone antagonists (41.0%/77.1%). In absolute terms, use of these therapies each increased by over 11% from admission. Ivabradine (11.5%/21.2%), automated internal cardiac defibrillators (29.5%/66.1%) and cardiac resynchronisation therapy (13.1%/28.7%) were used in a minority of eligible patients. Over the 1-year follow-up period, the mortality rate was 14.8%, and 44.2% of patients were readmitted to hospital at least once. CONCLUSION: Hospitalisation is a key mechanism for initiation of HFrEF therapies. The large evidence-practice gaps for ACEI/ARB and aldosterone antagonists represent potential avenues for improved HFrEF management.

COVID-19 and Acute Heart Failure: Screening the Critically Ill - A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ).

Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.

Obstructive sleep apnea and cardiovascular disease.

Obstructive sleep apnea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension and has also been implicated in the pathogenesis of congestive cardiac failure, pulmonary hypertension, arrhythmias, and atherosclerosis. Obesity is strongly linked to an increased risk of OSA, and weight loss can reduce the severity of OSA. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnea and the ensuing acute hemodynamic changes during sleep. Long-term CPAP treatment studies have shown a reduction in nocturnal cardiac ischemic episodes and improvements in daytime blood pressure levels and left ventricular function. Despite the availability of effective therapy, OSA remains an underdiagnosed and undertreated condition. A lack of physician awareness is one of the primary reasons for this deficit in diagnosis and treatment.

Repetitive hypoxia increases lipid loading in human macrophages-a potentially atherogenic effect.

Obstructive sleep apnea (OSA) is characterized by repetitive episodes of hypoxia and is associated with an increase in cardiovascular disease. We, therefore, investigated the effect of repetitive hypoxia on two key early events in atherogenesis; lipid loading in foam cells and monocyte adhesion to endothelial cells. Human macrophages were loaded with acetylated low-density lipoproteins. During lipid loading, the cells were exposed to 30 min cycles of 2%/21% oxygen or control (room air, 5% CO(2) incubator). Human umbilical vein endothelial cells (HUVECs) were also exposed to 30 min cycles of repetitive hypoxia or control conditions and monocyte adhesion measured. Cell adhesion molecules E-selectin, ICAM-1 and VCAM-1 were measured by ELISA. Repetitive hypoxia increased cholesteryl ester uptake by macrophages (127+/-5% compared to controls; p=0.003). By contrast, monocyte adhesion to HUVECs and cell adhesion molecule expression were unchanged by exposure to repetitive hypoxia, compared to controls (p >0.1). Repetitive hypoxia, at levels relevant to tissues such as the arterial wall, enhances lipid uptake into human macrophages. This may contribute to accelerated atherosclerosis in OSA patients.

Stable and unstable angina: Identifying novel markers on circulating leukocytes.

There is currently no blood-based test that can rapidly and objectively distinguish between chest pain which is initiated by increased myocardial oxygen demand (stable angina pectoris (SAP)) and chest pain initiated due to decreased coronary blood flow (unstable angina pectoris (UAP)). Since leukocytes play an active role in the progression of coronary artery disease (CAD), we hypothesize these can provide novel markers of SAP and UAP. Here we use a microarray of 82 cluster of differentiation (CD) antibodies (plus controls) to selectively immobilize peripheral blood mononuclear cells. We find that the pattern of leukocyte immobilization from patients with CAD significantly differs from healthy donors. Within the CAD group, 15 SAP patients exhibited significant (p<0.05) changes in 8 of 82 CD antibody spots compared to 19 age-matched healthy blood donors. An additional ten CD antigens differed between healthy donors and patients with UAP (p<0.05). Furthermore, seven CD antibody spots are significantly different between SAP and UAP patients. These preliminary data suggest it is now appropriate to undertake a larger clinical trial to test the hypothesis that these antibody microarrays can monitor the progression from SAP to UAP.

Treatment of obstructive sleep apnoea leads to enhanced pulmonary vascular nitric oxide release.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with pulmonary hypertension, however neither the pathogenesis of pulmonary vascular disease nor the effect of successful treatment of OSA on pulmonary vascular physiology has been characterised. METHODS: Seven subjects aged 52 (range 36-63) years with moderate to severe obstructive sleep apnoea (apnoea-hypopnoea index>15/h) had detailed pulmonary vascular reactivity studies, before and after 3 months of successful treatment with nasal continuous positive airways pressure (CPAP). On both occasions, we measured pulmonary pressure, flow velocity, flow and resistance, at baseline and in response to acetylcholine (an endothelium-dependent dilator), sodium nitroprusside (an endothelium-independent dilator), l-NMMA (an antagonist of nitric oxide synthesis) and l-Arginine (the substrate of nitric oxide). RESULTS: At baseline, pulmonary flow increased in response to acetylcholine and nitroprusside and fell in response to l-NMMA. Following CPAP treatment, the decrease in flow to l-NMMA was significantly greater (to 62+/-6% of control value vs 85+/-6% of pre-treatment; p=0.01), consistent with enhanced basal release of nitric oxide. The acetylcholine response tended to be greater after treatment (174+/-26% of control vs 147+/-12% of pre-CPAP, p=0.22), however the nitroprusside response was unchanged. CONCLUSION: Successful treatment of obstructive sleep apnoeic episodes in sleep results in enhanced nitric oxide release by the pulmonary microvascular circulation.

Nitric oxide does not mediate the vasodilation of early human pregnancy.

BACKGROUND: In early pregnancy, a substantial drop in arterial blood pressure occurs, that might be attributed to enhanced vascular nitric oxide synthesis. We investigated whether nitric oxide mediates the vasodilation that occurs in early human pregnancy. METHODS: Resting and stimulated forearm vascular resistance were measured (venous occlusion plethysmograph) in six women at 10 +/- 3 weeks of uncomplicated pregnancy and in the same women 7 +/- 5 weeks after elective termination of pregnancy. Forearm vascular resistance was also measured in six non-pregnant, healthy controls. RESULTS: Resting forearm vascular resistance was similar during pregnancy (33 +/- 16 arbitrary units (AU)), after pregnancy (31 +/- 10 AU) and in controls (41 +/- 13 AU, P > 0.05). The decreases in forearm vascular resistance to intrabrachial infusions of acetylcholine (2 and 20 microg/min), serotonin (10 and 100 ng/min) and sodium nitroprusside (1 and 2.5 microg/min) were similar in all groups. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine (16 micromol/min) produced similar increases in vascular resistance in pregnant women (38 +/- 17 AU), after pregnancy (36 +/- 14 AU) and in control subjects (42 +/- 8 AU, P = NS). CONCLUSIONS: These results indicate that neither basal nor stimulated nitric oxide levels are altered in the forearm circulation during first trimester pregnancy.