Vasoresponsiveness in patients with heart failure (VASOR): protocol for a prospective observational study.

BACKGROUND: Vasoplegia is a severe complication which may occur after cardiac surgery, particularly in patients with heart failure. It is a result of activation of vasodilator pathways, inactivation of vasoconstrictor pathways and the resistance to vasopressors. However, the precise etiology remains unclear. The aim of the Vasoresponsiveness in patients with heart failure (VASOR) study is to objectify and characterize the altered vasoresponsiveness in patients with heart failure, before, during and after heart failure surgery and to identify the etiological factors involved. METHODS: This is a prospective, observational study conducted at Leiden University Medical Center. Patients with and patients without heart failure undergoing cardiac surgery on cardiopulmonary bypass are enrolled. The study is divided in two inclusion phases. During phase 1, 18 patients with and 18 patients without heart failure are enrolled. The vascular reactivity in response to a vasoconstrictor (phenylephrine) and a vasodilator (nitroglycerin) is assessed in vivo on different timepoints. The response to phenylephrine is assessed on t1 (before induction), t2 (before induction, after start of cardiotropic drugs and/or vasopressors), t3 (after induction), t4 (15 min after cessation of cardiopulmonary bypass) and t5 (1 day post-operatively). The response to nitroglycerin is assessed on t1 and t5. Furthermore, a sample of pre-pericardial fat tissue, containing resistance arteries, is collected intraoperatively. The ex vivo vascular reactivity is assessed by constructing concentrations response curves to various vasoactive substances using isolated resistance arteries. Next, expression of signaling proteins and receptors is assessed using immunohistochemistry and mRNA analysis. Furthermore, the groups are compared with respect to levels of organic compounds that can influence the cardiovascular system (e.g. copeptin, (nor)epinephrine, ANP, BNP, NTproBNP, angiotensin II, cortisol, aldosterone, renin and VMA levels). During inclusion phase 2, only the ex vivo vascular reactivity test is performed in patients with (N = 12) and without heart failure (N = 12). DISCUSSION: Understanding the difference in vascular responsiveness between patients with and without heart failure in detail, might yield therapeutic options or development of preventive strategies for vasoplegia, leading to safer surgical interventions and improvement in outcome. TRIAL REGISTRATION: The Netherlands Trial Register (NTR), NTR5647. Registered 26 January 2016.

Vasoplegia After Restrictive Mitral Annuloplasty for Functional Mitral Regurgitation in Patients With Heart Failure.

OBJECTIVES: Patients undergoing heart failure surgery are at risk for developing postoperative vasoplegia. The aim of this study was to determine the incidence, survival, and predictors of vasoplegia in heart failure patients undergoing mitral valve repair for functional mitral regurgitation and to evaluate the effect of ischemic versus non-ischemic etiology. DESIGN: Retrospective. SETTING: University medical center, single institutional. PARTICIPANTS: Heart failure patients with functional mitral regurgitation who underwent restrictive mitral annuloplasty (2006-2015). MEASUREMENTS AND MAIN RESULTS: One hundred twenty-two patients were included (48% ischemic etiology). The incidence of vasoplegia was 19% and was not influenced by mitral regurgitation etiology. Ninety-day survival rate was decreased in vasoplegic compared with non-vasoplegic patients (65% v 93%, p < 0.001). After adjusting for age, gender, and heart failure etiology, prior hypertension (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.08-0.91; p = 0.034), higher creatinine clearance (OR 0.97; 95% CI 0.95-0.99; p = 0.009), and beta-blocker use (OR 0.25; 95% CI 0.09-0.73; p = 0.011) decreased the risk of vasoplegia. Anemia (OR 3.00; 95% CI 1.10-8.20; p = 0.032) and longer cross clamp (OR 1.03; 95% CI 1.01-1.04; p = 0.001), cardiopulmonary bypass (OR 1.01; 95% CI 1.00-1.02; p = 0.003), and procedure times (OR 1.01; 95% CI 1.00-1.02, p = 0.002) increased the risk of vasoplegia. CONCLUSIONS: Vasoplegia occurs in 19% of heart failure patients undergoing mitral valve repair for functional mitral regurgitation. It is associated with a poor early outcome. Prior hypertension, a higher creatinine clearance, and beta-blocker use were associated with a decreased risk of vasoplegia, whereas anemia and longer procedure times were associated with an increased risk of vasoplegia, independent of heart failure etiology.

Vasoplegia After Surgical Left Ventricular Restoration: 2-Year Follow-Up.

BACKGROUND: Vasoplegia is a severe complication that can develop after surgical procedures for heart failure. The current study evaluated the effect of vasoplegia on survival, cardiac function, and renal function 2 years after surgical left ventricular restoration (SVR). METHODS: Heart failure patients with a left ventricular ejection fraction (LVEF) of 0.35 or less who underwent SVR in 2006 to 2014 were included. Vasoplegia was defined as the continuous need of vasopressors (norepinephrine ≥0.2 µg · kg-1 · min-1 or terlipressin [any dose], or both) combined with a cardiac index of 2.2 L · min-1 · m-2 or higher for at least 12 consecutive hours, starting within the first 3 days postoperatively. The effect of vasoplegia on mortality, New York Heart Association Functional Classification, LVEF, and creatinine clearance was assessed up to 2 years of follow-up. RESULTS: SVR was performed in 113 patients (80% men), aged 62 ± 10 years, and with an LVEF of 0.25 ± 0.06. Postoperative vasoplegia developed in 23%. Survival was lower in patients with vasoplegia compared with patients without vasoplegia at 6 months (62% vs 90%, p = 0.001) and at 2 years (50% versus 84%, p < 0.001). At the 2-year follow-up, New York Heart Association class and LVEF had improved and were similar in both groups (respectively, p = 0.319 and p = 0.444). Creatinine clearance was lower in patients with vasoplegia compared with patients without vasoplegia 2 years postoperatively (p < 0.001), even after correcting for baseline creatinine clearance (p = 0.009). CONCLUSIONS: Vasoplegia after SVR is associated with decreased survival. Despite an improved and similar cardiac function, renal function was compromised in vasoplegic patients at the 2-year follow-up.

Electronic Nose Technology Fails to Sniff Out Acute Mountain Sickness.

Berendsen, Remco R., Marieke E. van Vessem, Marcel Bruins, Luc J.S.M. Teppema, Leon P.H.J. Aarts, and Bengt Kayser. Electronic nose technology fails to sniff out acute mountain sickness. High Alt Med Biol. 19:232-236, 2018. AIM: The aim of the study was to evaluate whether an electronic nose can discriminate between individuals with and without acute mountain sickness (AMS) following rapid ascent to 4554 m. RESULTS: We recruited recreational climbers (19 women, 82 men; age 35 ± 10 years, mean ± standard deviation [SD]) upon arrival at 4554 m (Capanna Regina Margherita, Italy) for a proof of concept study. AMS was assessed with the Lake Louise self-report score (LLSRS) and the abbreviated Environmental Symptoms Questionnaire (ESQc); scores ≥3 and ≥0.7 were considered AMS, respectively. Exhaled air was analyzed with an electronic nose (Aeonose; The eNose Company, Netherlands). The collected data were analyzed using an artificial neural network. AMS prevalence was 44% with the LLSRS (mean score of those sick 4.4 ± 1.4 [SD]) and 20% with the ESQc (1.2 ± 0.5). The electronic nose could not discriminate between AMS and no AMS (LLSRS p = 0.291; ESQc p = 0.805). CONCLUSION: The electronic nose technology utilized in this study could not discriminate between climbers with and without symptoms of AMS in the setting of an acute exposure to an altitude of 4554 m. At this stage, we cannot fully exclude that this technology per se is not able to discriminate for AMS. The quest for objective means to diagnose AMS thus continues.

Right ventricular dysfunction after surgical left ventricular restoration: prevalence, risk factors and clinical implications.

OBJECTIVES: Surgical left ventricular (LV) restoration (SVR) induces changes in LV systolic and diastolic function that may affect postoperative right ventricular (RV) function. This study aimed to evaluate the long-term effect of SVR on RV function, with specific focus on determinants and prognostic implications of RV dysfunction. METHODS: Eighty-six patients (age 60 ± 10 years, 73% male) with clinical and echocardiographic follow-up 2 years after SVR were included. RV dysfunction was defined as RV fractional area change <35%. The association between RV dysfunction at follow-up and clinical and echocardiographic characteristics and outcome was investigated. RESULTS: RV dysfunction at follow-up was present in 40% of patients and was associated with worse preoperative RV fractional area change (39 ± 9 vs 46 ± 7%, P < 0.01), pulmonary hypertension (18 vs 4%, P = 0.03) and higher follow-up LV filling pressures (E/E' ratio 23 ± 8 vs 15 ± 8, P = 0.02). At follow-up, patients with RV dysfunction were more frequently in New York Heart Association Class III or IV (30 vs 12%, P = 0.04) and 5-year mortality, heart transplantation and LV assist device implantation rate was increased (49 vs 17%, P < 0.01) as compared to patients with normal RV function. CONCLUSIONS: RV dysfunction after SVR was observed in 40% of patients and was associated with preoperative RV dysfunction, presence of pulmonary hypertension and an increase in LV filling pressures at follow-up. Patients with RV dysfunction after SVR had worse clinical functioning and outcome as compared to patients with normal RV function.

Incidence and predictors of vasoplegia after heart failure surgery.

Objectives: Vasoplegia has been described as a complication after cardiac surgery, particularly in patients with a poor left ventricular ejection fraction. The aim of this study was to assess the incidence, survival and predictors of vasoplegia in patients undergoing heart failure surgery and to propose a risk model. Methods: A retrospective study including heart failure patients who underwent surgical left ventricular restoration, CorCap implantation or left ventricular assist device implantation between 2006 and 2015. Patients were classified by the presence or absence of vasoplegia. Results: Two hundred and twenty-five patients were included. The incidence of vasoplegia was 29%. The 90-day survival rate in vasoplegic patients was lower compared with non-vasoplegic patients (71% vs 91%, P < 0.001). After adjusting for age, sex and surgical procedure, anaemia (OR 2.195; 95% CI 1.146, 4.204; P = 0.018) and a higher thyroxine level (OR 1.140; 95% CI 1.033, 1.259; P = 0.009) increased the risk of vasoplegia; a higher creatinine clearance (OR 0.980; 95% CI 0.965, 0.994; P = 0.006) and beta-blocker use (OR 0.257; 95% CI 0.112, 0.589; P = 0.001) decreased the risk. The risk model consisted of the same variables and could adequately identify patients at risk for vasoplegia. Conclusions: Vasoplegia after heart failure surgery is common and results in a lower survival rate. Anaemia and a higher thyroxine level are associated with an increased risk on vasoplegia. In contrast, a higher creatinine clearance and beta-blocker use decrease the risk on vasoplegia. These factors are used in the risk model that may guide treatment strategy.

Right ventricular dysfunction affects survival after surgical left ventricular restoration.

OBJECTIVE: Several clinical and left ventricular parameters have been associated with prognosis after surgical left ventricular restoration in patients with ischemic heart failure. The aim of this study was to determine the prognostic value of right ventricular function. METHODS: A total of 139 patients with ischemic heart failure (62 ± 10 years; 79% were male; left ventricular ejection fraction 27% ± 7%) underwent surgical left ventricular restoration. Biventricular function was assessed with echocardiography before surgery. The independent association between all-cause mortality and right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain was assessed. The additive effect of multiple impaired right ventricular parameters on mortality also was assessed. RESULTS: Baseline right ventricular fractional area change was 42% ± 9%, tricuspid annular plane systolic excursion was 18 ± 3 mm, and right ventricular longitudinal peak systolic strain was -24% ± 7%. Within 30 days after surgery, 15 patients died. Right ventricular fractional area change (hazard ratio, 0.93; 95% confidence interval, 0.88-0.98; P < .01), tricuspid annular plane systolic excursion (hazard ratio, 0.80; 95% confidence interval, 0.66-0.96; P = .02), and right ventricular longitudinal peak systolic strain (hazard ratio, 1.15; 95% confidence interval, 1.05-1.26; P < .01) were independently associated with 30-day mortality, after adjusting for left ventricular ejection fraction and aortic crossclamping time. Right ventricular function was impaired in 21%, 20%, and 27% of patients on the basis of right ventricular fractional area change, tricuspid annular plane systolic excursion, and right ventricular longitudinal peak systolic strain, respectively. Any echocardiographic parameter of right ventricular dysfunction was present in 39% of patients. The coexistence of several impaired right ventricular parameters per patient was independently associated with increased 30-day mortality (hazard ratio, 2.83; 95% confidence interval, 1.64-4.87, P < .01 per additional impaired parameter). CONCLUSIONS: Baseline right ventricular systolic dysfunction is independently associated with increased mortality in patients with ischemic heart failure undergoing surgical left ventricular restoration.