Attitudes of Patients with Advanced Chronic Illnesses Toward Palliative Extubation in a Country Where It Is Illegal.

Background: Palliative extubation (PE) is the cessation of mechanical ventilation (MV) during terminal illness. Although PE is widely practiced in many countries, it remains illegal in others. Attitudes toward PE of patients at the highest risk for MV were scarcely explored before. Objective: To assess the attitudes of patients with advanced chronic illnesses (ACI) toward PE and other end-of-life decisions in a country where PE is illegal. Design: A prospective observational study using questionnaire-based interviews. Setting/Subjects: Patients with ACI hospitalized between 2021 and 2022 in a large tertiary center. Attitudes toward PE and mechanical ventilation were evaluated. Predictors for favoring/opposing PE were analyzed using multivariate logistical regression models. Results: A total of 152 (40% female, 75 ± 11 years) patients were included. The most common ACIs were advanced heart failure (32%), metastatic malignancy (32%), and chronic obstructive pulmonary disease (22%). Around 132 patients (87%) supported the legalization of PE, and their main reason was to avoid pain and suffering (87%). Legalization of PE would change the decision to avoid mechanical intubation in 34% of the cases. Most patients thought that the decision to perform PE should be made by the patient's physician and primary caregiver collaboratively (64%). Religious observance was an independent predictor for opposing PE (adjusted odds ratio 0.18; 95% confidence interval 0.06-0.59; p < 0.01), whereas the type of ACI was not. Conclusion: Most admitted patients with ACIs support the legalization of PE. Such policy change could have major impact on patients' end-of-life preferences. At-risk patients should be the focus of future studies in this area.

Smoking and Respiratory Diseases in Patients with Coronary Microvascular Dysfunction.

BACKGROUND: Coronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence about their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. METHODS: This is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory. Patients with evidence of obstructive coronary artery disease or with missing data were excluded. Associations between respiratory-related variables and indices of CMD were assessed using univariate and multivariate regression models. RESULTS: Overall, 266 patients (mean age 67 ± 11 years, 59% females) were included in the current analysis. Of those, 155 (58%) had evidence of CMD. Among the respiratory variables, independent predictors of CMD were current smoking (adjusted odds ratio [AOR] 2.5; 95% confidence interval [CI], 1.2-5; P = .01) and obstructive sleep apnea (AOR 5.7; 95% CI, 1.2-26; P = .03), while chronic obstructive pulmonary disease was not. Among ever-smokers, higher smoking pack-years was an independent risk factor for CMD (median 35 vs 25 pack-years, AOR 1.09; 95% CI, 1.04-1.13; P < .01), and was associated with higher rates of pathologic index of microcirculatory resistance and resistive reserve ratio. CONCLUSION: In patients undergoing invasive coronary microvascular evaluation, current smoking and obstructive sleep apnea are independently associated with CMD. Among smokers, higher pack-years is a strong predictor for CMD. Our findings should raise awareness for prevention and possible treatment options.

Predictive value of elevated neutrophil gelatinase-associated lipocalin levels for assessment of in-hospital adverse outcomes among myocardial infarction patients.

BACKGROUND: Inflammatory biomarkers are known to rise and have predictive value for adverse outcomes in patients with acute coronary ischemia. One of those biomarkers is neutrophil gelatinase-associated lipocalin (NGAL). To date, only very few studies have assessed the prognostic value of NGAL in this setting. We investigated the prognostic utility of elevated NGAL levels on clinical outcomes among ST-elevation myocardial infarction patients. METHODS: High NGAL was defined as values within the 4th quartile. Patients were assessed for major in-hospital adverse clinical events (MACE). Multivariable logistic regression and area under the receiver operating characteristic curve (AUC) were used to further evaluate NGAL association for MACE and discrimination ability. RESULTS: A total of 273 patients were included. patients with high NGAL were at increased risk for MACE (62% vs. 19%; odds ratio 6.88, 95% confidence interval, 3.77-12.54, P  < 0.001). After propensity score matching, the incidence of MACE was significantly higher in patients with high vs. low NGAL levels (69% vs. 6%, P  = 0.002). In multivariable regression, high NGAL level was independently associated with MACE. The discrimination ability of NGAL to identify MACE (AUC 0.823), is significantly better than that of other inflammatory markers. CONCLUSION: Among ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, high NGAL levels are associated with adverse outcomes, independent of traditional inflammatory markers.

Intermittent inotropic therapy with levosimendan vs. milrinone in advanced heart failure patients.

AIMS: Routine, intermittent inotropic therapy (IIT) is still applied in advanced heart failure (HF) patients either as a bridge to definitive treatment or as a mean to improve quality of life (QOL), despite limited evidence to support its' use. Given recent reports of improved QOL and reduced HF hospitalization, with levosimendan compared with placebo in advanced HF patients, we aimed to assess the effects of switching a small group of milrinone-treated patients to levosimendan. This was performed as part of a protocol for changing our ambulatory HF clinic milrinone-based IIT to levosimendan. METHODS AND RESULTS: Single-centre study of consecutive ambulatory advanced HF patients that received ≥4 cycles of once-weekly milrinone IIT at our HF outpatient clinic, who were switched to levosimendan IIT. All patients had left ventricular ejection fraction ≤35%, elevated B-natriuretic peptide (BNP), and were in New York Heart Association Classes III-IV despite maximally tolerated guideline directed medical therapy. Patients were evaluated using BNP levels, echocardiography, cardio-pulmonary exercise test, and HF QOL questionnaire before and after 4 weeks of levosimendan IIT. The cohort included 11 patients, 10 (91%) were male and the mean age was 76 ± 12 years. After 4 weeks of levosimendan therapy, maximal O2 consumption improved in 8/9 (89%) by a mean of 2.28 mL/kg [95% CI -0.22-3.38, P = 0.05]. BNP levels decreased in 9/11 (82%) levosimendan treated patients, from a median of 1015 ng/L [261-1035] to 719 ng/L [294-739], (P < 0.01). QOL as measure by the EQ-5D-5L questionnaire improved in 8/11 (82%) patients after levosimendan IIT, by a median of two points [95% CO -4.14-0.37, P = 0.09]. On echocardiography, peak systolic annular velocity (S') increased after levosimendan IIT by an average of 3 cm/s [95% CI 0.16-2.10, P = 0.03]. CONCLUSIONS: In this small-scale study of ambulatory advanced HF patients, we observed improvements in right ventricular systolic function, maximal O2 consumption, and BNP after switching from milrinone to levosimendan based IIT.

Echocardiographic Killip Classification.

BACKGROUND: Although routine echocardiographic parameters such as ejection fraction are used to risk-stratify for death in patients referred for echocardiography, they have limited predictive value. The authors speculated that noninvasive hemodynamic echocardiographic data, assessing left ventricular filling pressure and output, stratified on the basis of the clinical Killip score, might have additive prognostic value on top of routine echocardiographic parameters. The authors created an echocardiographic correlate of this classification, using diastolic grade and stroke volume index (SVI) as indicators of pulmonary congestion and systemic perfusion, respectively, and evaluated the prognostic value of this correlate. METHODS: A retrospective study of consecutive patients (hospitalized or not) referred for echocardiography for a range of cardiac diagnoses in a tertiary medical center. A total of 556 patients in sinus rhythm who were evaluated by two sonographers, and reviewed by a single cardiologist, were included. Normal filling pressure and normal SVI (>35 mL/m2) defined echocardiographic Killip (eKillip) class 1. Patients with pseudonormal or restrictive diastolic patterns and normal SVI were ascribed to eKillip class 2 or 3, respectively. A pseudonormal or restrictive diastolic pattern and a subnormal SVI defined eKillip class 4. RESULTS: eKillip class 1 was present in 382 patients (68%); 115 (20%), 26 (5%), and 42 (7%) patients were in eKillip classes 2 to 4, respectively. Median follow-up time was 1,056 days (interquartile range, 729-1,390 days). A total of 105 deaths occurred. Univariate Cox regression analysis showed that eKillip class was associated with all-cause mortality; hazard ratios (HR) -2.73 (95% CI, 1.67-4.48), 3.19 (95% CI, 1.42-7.17), and 4.79 (95% CI, 2.58-8.89) for each eKillip class above 1 (P < .001). In a multivariate analysis adjusted for the Charlson comorbidity index, eKillip class remained independently associated with all-cause mortality (P = .04). CONCLUSIONS: eKillip class was associated with all-cause mortality among all patients undergoing echocardiography at a tertiary hospital.

Chewing versus Swallowing Ticagrelor to Accelerate Platelet Inhibition in Acute Coronary Syndrome - the CHEERS study. For The PLATIS (Platelets and Thrombosis in Sheba) Study Group.

It was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti-platelet therapy represents standard care for treating NSTEMI patients. Ticagrelor is a direct acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Fifty NSTEMI patients were randomised to receive either a chewing loading dose of 180 mg ticagrelor or an equal standard oral dose of ticagrelor. Platelet reactivity was evaluated by VerifyNow at baseline, 1 and 4 h post-loading dose. Results are reported in P2Y12 reaction units. Patients then continued to receive standard 90 mg oral ticagrelor twice daily. Baseline characteristics did not differ between the two groups. P2Y12 reaction units in the chewing group compared with the standard group at 0, 1 and 4 h after ticagrelor loading dose were: 245 vs 239 (p=0.59), 45 vs 130 (p=0.001) and 39 vs 60 (p=0.12), respectively, corresponding to a relative inhibition of platelet aggregation of 83 % vs only 47 % at 1 h (p< 0.001), and 84 % vs 77 % (p=0.59) at 4 h. Major adverse cardiac and cardiovascular events at 30 days were low (2 %), occurring in only one patient in the standard group. In conclusion, chewing a 180 mg ticagrelor loading dose is feasible and facilitates both faster and improved early inhibition of platelet aggregation in NSTEMI patients, compared with a standard oral-loading dose.