Hemodynamic Responders Research Articles

Echocardiographic profiles and hemodynamic response after vasopressin initiation in septic shock: A cross-sectional study

PurposeVasopressin, used as a catecholamine adjunct, is a vasoconstrictor that may be detrimental in some hemodynamic profiles, particularly left ventricular (LV) systolic dysfunction. This study tested the hypothesis that echocardiographic parameters differ between patients with a hemodynamic response after vasopressin initiation and those without a response. MethodsThis retrospective, single-center, cross-sectional study included adults with septic shock receiving catecholamines and vasopressin with an echocardiogram performed after shock onset but before vasopressin initiation. Patients were grouped by hemodynamic response, defined as decreased catecholamine dosage with mean arterial pressure ≥ 65 mmHg six hours after vasopressin initiation, with echocardiographic parameters compared. LV systolic dysfunction was defined as LV ejection fraction (LVEF) <45%. ResultsOf 129 included patients, 72 (56%) were hemodynamic responders. Hemodynamic responders, versus non-responders, had higher LVEF (61% [55%,68%] vs. 55% [40%,65%]; p = 0.02) and less-frequent LV systolic dysfunction (absolute difference −16%; 95% CI −30%,−2%). Higher LVEF was associated with higher odds of hemodynamic response (for each LVEF 10%, response OR 1.32; 95% CI 1.04–1.68). Patients with LV systolic dysfunction, versus without LV systolic dysfunction, had higher mortality risk (HR(t) = e[0.81–0.1*t]; at t = 0, HR 2.24; 95% CI 1.08–4.64). ConclusionsPre-drug echocardiographic profiles differed in hemodynamic responders after vasopressin initiation versus non-responders.

Biventricular endocardial pacing and left bundle branch area pacing for cardiac resynchronization: Mechanistic insights from electrocardiographic imaging, acute hemodynamic response, and magnetic resonance imaging

Biventricular endocardial pacing (BiV-endo) has demonstrated superior cardiac resynchronization compared to conventional biventricular epicardial pacing (BiV-epi). Left bundle branch area pacing (LBBAP) may also achieve effective cardiac resynchronization therapy (CRT). The purpose of this study was to compare the acute electrical and hemodynamic effects of BiV-epi, BiV-endo, and LBBAP delivered from the LV endocardium and to assess how myocardial scar affects response. Eleven patients with heart failure and indications for CRT underwent a temporary pacing study with electrocardiographic imaging (ECGi) and hemodynamic assessment. BiV-endo was delivered by stimulation of the left ventricular (LV) lateral wall, and LBBAP was delivered by stimulation of the LV septum, at the site of a Purkinje potential. LV activation time (LVAT-95), LV dyssynchrony index (LVDI), biventricular activation time (BIVAT-90), and biventricular dyssynchrony index (BIVDI) were calculated. Myocardial scar was assessed using magnetic resonance imaging (MRI). The protocol was completed in 10 patients. Compared to BiV-epi (LVAT-95: 79.2 ± 13.1 ms; LVDI: 26.6 ± 3.4 ms) LV resynchronization was superior during BiV-endo (LVAT-95: 48.5 ± 14.9 ms; P = .001; LVDI: 16.6 ± 6.4 ms; P = .002) and LBBAP (LVAT-95: 48.9 ± 12.5 ms; P = .001; LVDI: 15.3 ± 3.4 ms; P = .001). Biventricular resynchronization was similarly superior during BiV-endo and LBBAP vs BiV-epi (BIVAT-90 and BIVDI; P <.05). The rate of acute hemodynamic responders was higher during BiV-endo (90%) and LBBAP (70%) vs BiV-epi (50%). The benefits of LBBAP (but not BiV-endo) on LV resynchronization were attenuated when septal scar was present in a subset of 8 patients who underwent MRI. Our findings suggest superior electrical resynchronization and a higher proportion of acute hemodynamic responders during BiV-endo and LBBAP compared to BiV-epi. Electrical resynchronization was similar between BiV-endo and LBBAP; however, septal scar seemed to attenuate response to LBBAP.

Cardiac power output index to define hemodynamic response to Impella support in cardiogenic shock.

Early assessment of response to Impella in cardiogenic shock may guide escalation of mechanical circulatory support. Therapeutic goal and response to Impella have not previously been defined. This study tested the hypothesis that targeting 3-h post- Impella cardiac power output index (CPOi)-"hemodynamic response"-in cardiogenic shock is associated with 12-h lactate clearance. Single-center study of 37 consecutive patients who underwent left-sided Impella support for cardiogenic shock due to either acute myocardial infarction or decompensated heart failure. Patients who achieved 3-h post-Impella CPOi ⩾ 0.30 W/m2 were defined as Impella "hemodynamic responder." Twelve of the thirty-seven patients achieved 3-h post-impella CPOi ⩾ 0.30 W/m2 ("hemodynamic responders"). Post-Impella CPOi correlated with 12-h lactate (r = -0.779, p < 0.001) and lactate clearance (r = 0.747, p < 0.001). "Hemodynamic responders" had lower 12-h lactate level and greater 12-h lactate clearance (52 (44-58) vs 17 (14-26)%, p < 0.001). Higher pre-Impella norepinephrine dose (-0.341, p = 0.003) and baseline lactate (-0.009, p = 0.003) were independently associated with lower 3-h post-Impella CPOi. Eighteen patients died within 30 days (2/12 "hemodynamic responders" compared to 16/25 "non-responders," p < 0.001). Patients who achieved early 3-h post-Impella CPOi of ⩾0.30 W/m2 have greater lactate clearance and better short-term survival. Early post-Impella CPOi of 0.30 W/m2 may be used as a therapeutic goal and define favorable response to Impella in cardiogenic shock.

Proportional Pulmonary Artery Pulse Pressure Identifies Hemodynamic Response to Impella: Conceptualization and Clinical Validation

<h3>Purpose</h3> <b>1.</b> To describe the physiologic determinants of proportional pulmonary artery pulse pressure (= ratio of pulmonary pulse pressure to mean pulmonary pressure, PP-MPAP) <b>2.</b> clinical application of PP-MPAP in patients with cardiogenic shock (CS) who underwent left-sided Impella support. <h3>Methods</h3> <b>1.</b> Using established physiologic concepts and prior data, the change in PP-MPAP a was modelled over a range of hemodynamic parameters (Matlab, Mathworks). <b>2.</b> 16 patients with CS who underwent Impella support were included. Hemodynamic responder was defined as increase in cardiac power output index (CPOi)>20%. Clinical endpoint was lactate clearance 12 hours after Impella support. <h3>Results</h3> <b>1.</b> The relationship between stroke volume at different heart rates and PAWP was modelled [FIGURE]. <b>2.</b> 16 patients were included (age: 50±7 years; 13/16 males; 9/16 acute MI; 7/16 cardiomyopathy; LVEF: 17±4%). Impella reduced PAWP in all patients, but only 6/16 patients were responders. As predicted by the model, PP-MPAP increased in responders but dropped in non-responders. The increase in PP-MPAP correlated with increase in CPOi. The 10 non-responders were escalated to Ecpella (3(2-5)hours post-Impella), which increased PP-MPAP [TABLE]. 12-hour lactate clearance was greater in responders despite escalation to Ecpella in non-responders. Post-support PP-MPAP and the change in PP-MPAP were significantly associated with 12-hour lactate clearance. <h3>Conclusion</h3> PP-MPAP has a predictable relationship with stroke volume, and can identify hemodynamic responders to Impella, who had higher 12-hour lactate clearance.

Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial

ObjectivesThe purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF). BackgroundThere are no proven effective treatments for patients with PH-HFpEF. MethodsPatients with mean pulmonary artery pressure (mPAP) ≥35 mm Hg, pulmonary capillary wedge pressure (PCWP) ≥20 mm Hg, and LVEF ≥40% underwent 6MWD and hemodynamic measurements at rest, during passive leg raise, and supine cycle exercise at baseline and after an open-label 24-h levosimendan infusion (0.1 μg/kg/min). Hemodynamic responders (those with ≥4 mm Hg reduction of exercise-PCWP) were randomized (double blind) to weekly levosimendan infusion (0.075 to 0.1 ug/kg/min for 24 h) or placebo for 5 additional weeks. The primary end point was exercise-PCWP, and key secondary end points included 6MWD and PCWP measured across all exercise stages. ResultsThirty-seven of 44 patients (84%) met responder criteria and were randomized to levosimendan (n = 18) or placebo (n = 19). Participants were 69 ± 9 years of age, 61% female, and with resting mPAP 41.0 ± 9.3 mm Hg and exercise-PCWP 36.8 ± 11.3 mm Hg. Compared with placebo, levosimendan did not significantly reduce the primary end point of exercise-PCWP at 6 weeks (−1.4 mm Hg; 95% confidence interval [CI]: −7.8 to 4.8; p = 0.65). However, levosimendan reduced PCWP measured across all exercise stages (−3.9 ± 2.0 mm Hg; p = 0.047). Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo. ConclusionsSix weeks of once-weekly levosimendan infusion did not affect exercise-PCWP but did reduce PCWP incorporating data from rest and exercise, in tandem with increased 6MWD. Further study of levosimendan is warranted as a therapeutic option for PH-HFpEF. (Hemodynamic Evaluation of Levosimendan in Patients With PH-HFpEF [HELP]; NCT03541603)

Levosimendan Improves Hemodynamics And Submaximal Exercise Capacity In Ph-hfpef: Primary Results From The Help-ph-hfpef Multicenter Randomized Controlled Trial

Introduction There is currently no effective treatment for patients with HFpEF and pulmonary hypertension (PH-HFpEF). We hypothesized that levosimendan (LEVO), a calcium sensitizer with inotropic and vascular smooth muscle relaxant properties, would improve hemodynamics and exercise capacity in PH-HFpEF. Methods We conducted a multicenter, double-blind, placebo-controlled trial testing the effects of once-weekly IV LEVO on hemodynamics and 6 minute walk distance (6MWD) in patients with PH-HFpEF. Participants with mean pulmonary artery (mPAP) ≥35 mmHg, PCWP ≥20 mmHg, LVEF ≥40% and NYHA II-III symptoms underwent 6MW and invasive hemodynamic assessments at rest, passive leg raise (PLR) and supine cycle exercise (EX) at baseline and following a 24-hour infusion of LEVO (0.1 μg/kg/min). Hemodynamic responders, defined as those with ≥4 mmHg reduction of EX PCWP, were then randomized, double blind, to a once weekly infusion of LEVO (up to 0.1 μg/kg/min) or placebo for 6 weeks, at which point hemodynamic assessments and 6MW test were repeated. The primary endpoint was between-group difference in the change of EX PCWP. Results Of 44 subjects enrolled, 37 (84%) qualified as responders and were randomized to LEVO (n=18) or placebo (n=19). Patients (69±9 years old, 61% women) displayed severe combined pre- and post-capillary PH at baseline (resting mPAP 41±10, PCWP 25±6 mmHg pulmonary vascular resistance 3.4±2.7). At 6-weeks, LEVO had no significant effect on EX PCWP compared to placebo (-1.4 mmHg, 95% CI, -7.7 to 4.8, p=0.65). However, in a mixed-effect repeated measure regression analysis incorporating rest, PLR, and EX stages, LEVO reduced PCWP by 3.9±2.0 mmHg as compared to placebo (p=0.047, Figure). As compared to placebo, LEVO improved 6MWD by 29 m (95% CI, 3 to 56, p=0.033). LEVO was well-tolerated with no difference in the incidence of adverse events compared to placebo. Conclusions In patients with PH-HFpEF, once-weekly treatment with LEVO for 6 weeks reduced PCWP and increased 6MWD without adverse effects. A phase 3 study to definitively test the safety and efficacy of LEVO as a treatment for PH-HFpEF is warranted.

Vasopressin Plasma Concentrations Are Not Associated with Hemodynamic Response to Exogenous Vasopressin for Septic Shock.

Positive hemodynamic response to vasopressin after 6hours of infusion was independently associated with lower mortality in a previous retrospective study of patients with septic shock. However, factors previouslyassociated with higher plasma vasopressin concentration were not associated with response, and the relationship between plasma vasopressin concentration and hemodynamic response has not been evaluated. This cross-sectional study compared plasma vasopressin concentrations in hemodynamic responders and nonresponders tovasopressin in patients with septic shock to evaluate plasma vasopressin concentration as a therapeutic target for hemodynamic response to vasopressin. Adult patients with septic shock were included if they were treated with fixed-dose vasopressin as an adjunct to catecholamines for at least 3hours. Patients were assigned to groups based on vasopressin response. Ten hemodynamic responders to vasopressin and eight nonresponders were included. Blood samples for plasma vasopressin concentration were collected 3-6hours after vasopressin initiation. Baseline characteristics were similar between groups. No difference was detected in plasma vasopressin concentrations between hemodynamic responders and nonresponders (median 88.6pg/ml [interquartile range (IQR) 84.4-107.5pg/ml] vs 89.9pg/ml [IQR 67.5-157.4pg/ml], p=0.79, respectively). We also did not detect a difference between groups after correcting for vasopressin dose; median vasopressin plasma concentration per 0.01 units/minute of vasopressin infusion for responders was 25.9pg/ml (IQR 21.8-31.8pg/ml) versus 29.5pg/ml (IQR 23.0-57.5pg/ml, p=0.48) for nonresponders. No difference in clinical outcomes was detected between groups. The findings were robust to multiple sensitivity analyses. This study does not support the use of plasma vasopressin concentrations as a therapeutic target to predict hemodynamic response to exogenous vasopressin in septic shock.

Contractility surrogates derived from three-dimensional lead motion analysis and prediction of acute haemodynamic response to CRT

BackgroundPatient-specific left ventricular (LV) lead optimisation strategies with immediate feedback on cardiac resynchronisation therapy (CRT) effectiveness are needed. The purpose of this study was to compare contractility surrogates derived from...

Does Acute Hemodynamic Response to Carvedilol in Hepatic Venous Pressure Gradient Predicts Morbidity and Mortality in Cirrhosis? Prospective Study

Background: Portal hypertension leads to most of the complication of cirrhosis: both bleeding and non-bleeding. Most complications due to portal hypertension can be ameliorated by β-blockers in those who are hemodynamic responders. To identify hemodynamic responder, a repeat hepatic venous pressure gradient (HVPG) is required 4–6 weeks after initiation of beta-blocker therapy. Acute hemodynamic response is a recent modality of determining HVPG response immediately during the baseline HVPG by giving high dose of injectable or oral beta-blocker. Aims: To assess the acute effect of Carvedilol on HVPG and its impact on outcome in cirrhotics over a 6-month period of follow up. Patients and Methods: Patients requiring β-blocker therapy, for primary (25/69) or secondary (44/69) prevention of variceal bleeding, were subjected to HVPG measurement. Acute Responder were defined as HVPG <12 mmHg or >10% fall in HVPG from baseline. Immediately after HVPG they were given Tab. Carvedilol 25 mg and a repeat HVPG was performed after one hour. On the basis of hemodynamic response 2 groups were made, Acute responders and non-responders. Both these groups were followed for 6 months. A repeat HVPG was done in acute responder group after 6 month. Both these group of patients were offered standard medical therapy with beta-blocker (Carvedilol) and regular EVL. All complications, hospitalization and outcome of patient noted at the end of 6 month. Results: Out of 69 patients, 49 (71%) patients showed acute reduction in HVPG of >10% after oral Carvedilol. There were no baseline differences between the two groups. On follow-up, complications like ascites was significantly less common in acute responder group as compared to non-responder group (P < 0.001). However, there was no statistically significant difference in mortality between acute responder and non-responder groups (P > 0.05). Repeat HVPG after a median period of 6 months could be performed in 41 of 49 patients in the acute responder group, while 2 patients was not willing for a repeat HVPG and 6 patients had died during this period. Out of 41 patients 35 (85%) patients were still responders (long term responders) and 6 (15%) patient were non long term responders. Conclusions: Determination of acute response to carvedilol is not only a convenient and rapid way to identify beta-blocker hemodynamic responders; it also is an excellent prognostic marker as acute responders develop less portal hypertensive complication like ascites than non-responders on beta-blocker therapy. Also the most of acute responders are found to be longstanding responder. Keywords: HVPG; portal hypertension; cirrhosis; esophageal varices

Zolmitriptan: A Novel Portal Hypotensive Agent Which Synergizes with Propranolol in Lowering Portal Pressure

ObjectiveOnly a limited proportion of patients needing pharmacological control of portal hypertension are hemodynamic responders to propranolol. Here we analyzed the effects of zolmitriptan on portal pressure and its potential interaction with propranolol.MethodsZolmitriptan, propranolol or both were tested in two rat models of portal hypertension: common bile duct ligation (CBDL) and CCl4-induced cirrhosis. In these animals we measured different hemodynamic parameters including portal venous pressure, arterial renal flow, portal blood flow and cardiac output. We also studied the changes in superior mesenteric artery perfusion pressure and in arterial wall cAMP levels induced by zolmitriptan, propranolol or both. Moreover, we determined the effect of splanchnic sympathectomy on the response of PVP to zolmitriptan.ResultsIn both models of portal hypertension zolmitriptan induced a dose-dependent transient descent of portal pressure accompanied by reduction of portal flow with only slight decrease in renal flow. In cirrhotic rats, splanchnic sympathectomy intensified and prolonged zolmitriptan-induced portal pressure descent. Also, propranolol caused more intense and durable portal pressure fall when combined with zolmitriptan. Mesenteric artery perfusion pressure peaked for about 1 min upon zolmitriptan administration but showed no change with propranolol. However propranolol enhanced and prolonged the elevation in mesenteric artery perfusion pressure induced by zolmitriptan. In vitro studies showed that propranolol prevented the inhibitory effects of β2-agonists on zolmitriptan-induced vasoconstriction and the combination of propranolol and zolmitriptan significantly reduced the elevation of cAMP caused by β2-agonists.ConclusionZolmitriptan reduces portal hypertension and non-selective beta-blockers can improve this effect. Combination therapy deserves consideration for patients with portal hypertension failing to respond to non-selective beta-blockers.

Non-selective betablocker therapy decreases intestinal permeability and serum levels of LBP and IL-6 in patients with cirrhosis

We evaluated the gastrointestinal permeability and bacterial translocation in cirrhotic patients with portal hypertension (PHT) prior to and after non-selective betablocker (NSBB) treatment. Hepatic venous pressure gradient (HVPG) was measured prior to and under NSBB treatment. Gastroduodenal and intestinal permeability was assessed by the sucrose-lactulose-mannitol (SLM) test. Anti-gliadin and anti-endomysial antibodies were measured. Levels of LPS-binding protein (LBP) and interleukin-6 (IL-6) were quantified by ELISA, and NOD2 and toll-like receptor 2 (TLR2) polymorphisms were genotyped. Fifty cirrhotics were included (72% male, 18% ascites, 60% alcoholic etiology). Abnormal gastroduodenal and intestinal permeability was found in 72% and 59% of patients, respectively. Patients with severe portal hypertension (HVPG ≥20 mm Hg; n=35) had increased markers of gastroduodenal/intestinal permeability (urine sucrose levels p=0.049; sucrose/mannitol ratios p=0.007; intestinal permeability indices p=0.002), and bacterial translocation (LBP p=0.002; IL-6 p=0.025) than patients with HVPG <20 mm Hg. A substantial portion of patients showed elevated levels of anti-gliadin antibodies (IgA: 60%, IgG: 34%) whereas no anti-endomysial antibodies were detected. A significant correlation of portal pressure (i.e., HVPG) with all markers of gastroduodenal/intestinal permeability and with LBP and IL-6 levels was observed. NOD2 and TLR2 risk variants were associated with abnormal intestinal permeability and elevated markers of bacterial translocation. At follow-up HVPG measurements under NSBB, we found an amelioration of gastroduodenal/intestinal permeability and a decrease of bacterial translocation (LBP - 16% p=0.018; IL-6 - 41% p<0.0001) levels, which was not limited to hemodynamic responders. Abnormal SLM test results and higher LBP/IL-6 levels were associated with a higher risk of variceal bleeding during follow-up but not with mortality. Abnormal gastroduodenal/intestinal permeability, anti-gliadin antibodies, and bacterial translocation are common findings in cirrhotic patients and are correlated with the degree of portal hypertension. NSBB treatment ameliorates gastroduodenal/intestinal permeability and reduces bacterial translocation partially independent of their hemodynamic effects on portal pressure, which may contribute to a reduced risk of variceal bleeding.

Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol

ObjectiveNon-selective β-blockers or endoscopic band ligation (EBL) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Additional α-adrenergic blockade (as by carvedilol) may increase the number...

Letter: sorafenib in portal hypertension – authors' reply

We are thankful to Procopet et al. for their comments and for sharing their data with us.1 We are also happy to see that our results2 were confirmed by an independent series and found a similar proportion of patients responding to treatment as we did. In addition, they were able to show a long-term effect of sorafenib on portal hypertension in some patients. We were unable to do so because our patients underwent trans-arterial chemoembolisation after 2 weeks of sorafenib treatment,3 which precluded us from obtaining unbiased hepatic venous pressure gradient (HVPG)-measurements and survival data thereafter. We are not surprised to see a lack of correlation between HVPG-response and survival, considering the overall patient number was 18, 11 patients underwent repeat HVPG-measurement only, and 4 of those showed a drop in HVPG. In view of the potential confounders in cirrhotic patients with hepatocellular carcinoma (HCC) with major impact on survival (cirrhosis stage, performance status, tumour size, vascular invasion, extrahepatic spread, among others), it would be really astonishing to find a significant survival difference within such a small patient sample. However, the findings extend nicely the principle observation from animal experiments4 to the clinical setting, with about one-third of treated individuals showing an improvement in portal hypertension with sorafenib, an effect of about the same magnitude as can be expected from the treatment of portal hypertensive patients with nonselective β-blockers like propranolol or nadolol.5 We agree with Procopet et al. that for studying the antihypertensive effects of sorafenib, patients with HCC are not an ideal patient population, but for lack of other options to test the drug so far, both of our groups did resort to this group of patients to perform a proof-of-principle study on the haemodynamic effects of sorafenib in humans. In our opinion, two scenarios for the use of sorafenib for treatment of portal hypertension could be envisioned: as variceal bleeding is a major cause of death in patients with advanced stage HCC, haemodynamic responders to sorafenib might not need the addition of a nonselective β-blocker for prevention of variceal bleeding, which could help to improve their quality of life significantly. On the other hand, in cirrhotic patients without HCC and nonresponse to nonselective β-blockers, lower dose sorafenib (for safety and tolerability reasons) could be investigated as an alternative medical treatment option (albeit currently not feasible for economic reasons). We think that in view of the human data presented as well as our previous preclinical data from a model of prehepatic portal hypertension,6 a pilot trial on the effects of lower dose sorafenib on portal hypertension in patients with cirrhosis would be reasonable, in particular, in patients not responding to nonselective β-blockers. Prospective randomised trials do not seem to be warranted to date as long as we do not have data on the response in this selected and difficult to treat patient group. The authors' declarations of personal and financial interests are unchanged from those in the original article.2

Long-term follow-up of hemodynamic responders to pharmacological therapy after variceal bleeding

Although it is assumed that hemodynamic responders to pharmacological therapy after a variceal hemorrhage are adequately protected from rebleeding, there is no evidence that either this response or its protective effect extend beyond the usual 2-year follow-up featured in available studies. We aimed to assess the maintenance of hemodynamic response and its impact on outcomes in a large cohort of hemodynamic responders during a long follow-up. One hundred three patients with cirrhosis admitted with acute variceal bleeding between 2001 and 2010 were prospectively evaluated. The hepatic venous pressure gradient (HVPG) was determined 5 days after the bleeding and repeated 5-7 days after maximal tolerated doses of nadolol and nitrates. Hemodynamic responders (HVPG ≤ 12 mm Hg or ≥ 20% decrease from baseline) were maintained on drugs and followed up with annual HVPG measurements. Forty-eight patients (47%) were hemodynamic responders. The median follow-up was 48 months (range, 2-108 months). Long-term HVPG evaluations could not be performed in eight patients (four deaths, two rebleedings, two follow-ups <1 year). Among the remaining 40 patients, hemodynamic response was maintained in 26 (65%) and lost in 14 (35%). There were no baseline differences between the two subgroups. However, 100% of alcoholic patients who remained abstinent maintained long-term response, compared with 36% of nonabstinent alcoholics and 50% of patients with viral cirrhosis. Patients with loss of hemodynamic response rebled more during follow-up and showed a higher incidence of death or liver transplantation. After variceal bleeding, long-term maintenance of hemodynamic response to drug therapy is mainly restricted to patients with alcoholic cirrhosis who remain abstinent. The loss of this long-term response carries worse clinical outcomes.

In the Resuscitation of Hemorrhagic Shock, Transient Hemodynamic Responders Have a Higher Acute Mortality and an Altered Inflammatory Response Compared to Definitive Responders

In the Resuscitation of Hemorrhagic Shock, Transient Hemodynamic Responders Have a Higher Acute Mortality and an Altered Inflammatory Response Compared to Definitive Responders

Non-selective β-blockers improve the correlation of liver stiffness and portal pressure in advanced cirrhosis

Liver stiffness (LS) correlates with portal pressure (hepatic venous pressure gradient, HVPG). However, the dynamic components of portal hypertension (PHT) in advanced cirrhosis may not be adequately assessed by TE. The influence of treatment with non-selective β-blockers (NSBB) on the correlation of HVPG and LS has not been investigated. One hundred and twenty-two patients with esophageal varices were included. LS, hemodynamic parameters, and HVPG were recorded at baseline (BL) and after 6 weeks of treatment with NSBB (FU). The correlation of LS and HVPG was compared to control patients with HVPG ≤ 12 mmHg. Patients with higher Child-Pugh stages (A:88/B:25/C:9) had higher levels of liver stiffness (47.4 ± 16.5 vs. 70.3 ± 7.9 vs. 73.7 ± 2.1 kPa) and HVPG (21 ± 5 vs. 26 ± 5 vs. 26 ± 4 mmHg). The correlation of LS and HVPG was stronger in controls with HVPG ≤ 12 mmHg (R = 0.951; P < 0.0001) than in patients with HVPG > 12 mmHg (R = 0.538; P = 0.0004). The association of HVPG with LS became stronger under treatment with NSBB, which finally restored the linear correlation of HVPG and LS (R = 0.930; P < 0.0001). Forty-three percent (53/122) of patients were hemodynamic responders to NSBB. The improvement in the correlation of LS and HVPG under NSBB was mainly noted in hemodynamic responders (R = 0.864), but not in nonresponders (R = 0.535), whereas changes in LS, heart rate, and MAP were similar in responders and nonresponders. Targeting the hyperdynamic circulation and the increased splanchnic blood inflow by treatment with NSBB unmasks the linear (mechanical) correlation of HVPG and LS in patients with HVPG > 12 mmHg. Measurement of LS by TE is not a feasible method to assess the dynamic components of PHT.

Clinical and Procedural Characteristics of Acute Hemodynamic Responders Undergoing Triple-Site Ventricular Pacing for Advanced Heart Failure

The advantages of triple-site ventricular pacing (Tri-V) compared to conventional biventricular site pacing (Bi-V) have been reported. We sought to identify the predictors of acute hemodynamic Tri-V responders. Acute hemodynamic studies were performed in 32 patients with advanced heart failure during Tri-V implantation. After the right ventricular (RV) and left ventricular (LV) leads were implanted for a conventional Bi-V system, an additional pacing lead was implanted in the RV outflow tract for Tri-V. The LV peak +dP/dt and tau were measured during AAI, Bi-V, and Tri-V pacing. A Tri-V responder was defined as a patient whose percentage of increase in the peak +dP/dt during Tri-V was >10% compared to of that during Bi-V. The baseline clinical variables and RV outflow tract lead location were analyzed to identify the characteristics of the Tri-V responders. Of the 32 patients, 10 (31%) were classified as Tri-V responders. The LV end-diastolic volume was greater (246 ± 48 vs 173 ± 53 ml, p <0.01), and the RV outflow tract lead was implanted at a greater outflow tract portion (p <0.05) in the Tri-V responders. Multivariate analysis revealed that only the baseline LV end-diastolic volume (per 50-ml greater) predicted the Tri-V response (odds ratio 2.87, 95% confidence interval 1.03 to 8.00, p <0.05). The area under the receiver operating characteristic curve for the LV end-diastolic volume was 0.84 (p <0.01) and an LV end-diastolic volume of >212 ml had a sensitivity of 80% and specificity of 77% to distinguish Tri-V responders. In conclusion, Tri-V provides greater hemodynamic effect for patients with a larger LV end-diastolic volume owing to its resynchronization effects on the LV anterior wall.

Predictors of postoperative outcome after pulmonary endarterectomy from a 14-year experience with 279 patients

Postoperative outcome after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is difficult to predict. We sought to analyze specific preoperative findings to predict mortality, shorter mechanical ventilation, and hemodynamic improvement after PEA. A total of 279 patients with CTEPH (57 ± 14 years old, 57% male), who underwent PEA between 1995 and 2009, were reviewed retrospectively. Preoperative pulmonary hemodynamic parameters, spirometry data, laboratory data, cardiac co-morbidities, clinical stage, and number of desobliterated segments were analyzed using a logistic regression model to identify independent predictors for early mortality, shorter duration of mechanical ventilation, and hemodynamic improvement. There were 31 early deaths (11.1%, last three years: 6.7%). Among 16 significant predictors for early mortality, preoperative arterial oxygenation was the only significant predictor in multivariate analysis (P < 0.05). A total of 147 patients (52.7%) could be extubated within 48 h postoperatively. Out of 16 significant predictors in univariate analysis for mechanical ventilation less than 48 h, only higher forced expiratory volume in 1s FEV1.0 (P < 0.05) and higher preoperative cardiac index (P < 0.05) were significant in multivariate analysis. In 185 patients (66.3%), postoperative pulmonary vascular resistance (PVR) was reduced to lower than 400 dyn s(-1) cm(-5) at 48 h after PEA. Male gender (P < 0.05), lower preoperative mean pulmonary arterial pressure (PAP) (P < 0.05), and more intra-operative desobliterated segments (P < 0.01) were identified as significant predictors for this hemodynamic response with sensitivity of 77.5% and specificity of 67.9%. Using Pearson's correlation coefficient, PVR at 48 h after PEA could be estimated as PVR = 123.266+135.471 × creatinine-22.053 × desobliterated segments + 3.248 × systolic PAP (P < 0.01, R(2) = 0.401, 95% confidence interval = 0.464-0.830). Preoperative factors can primarily predict postoperative outcome after PEA. Patients with underlying parenchymal lung disease will have increased risk for early mortality and prolonged mechanical ventilation. The extent of desobliterated segments as well as preoperative hemodynamic severity play a key role in predicting good hemodynamic responders.

β‐Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta‐analysis

Bacterial infections have been hypothetized to be a trigger of variceal bleeding in cirrhotic patients and beta-blockers may have a protective effect by decreasing bacterial translocation, reducing portal pressure. The aim of our study was to evaluate the possible role of beta-blockers in preventing spontaneous bacterial peritonitis (SBP) in patients with liver cirrhosis and ascites. Extensive search of the literature including randomized controlled trial (RCT) and non-RCT of primary and secondary prophylaxis for variceal bleeding in cirrhotics using beta-blockers were evaluated. We performed a meta-analysis using the occurrence of SBP as endpoint in all the studies, using the random effect model. Three RCT and three retrospective studies in which beta-blockers were evaluated against no treatment for the prevention of SBP in ascitic cirrhotics were included. There was a statistically significant difference of 12.1%, P<0.001 in favour of propranolol in preventing SBP, which was confirmed by sensitivity analysis evaluating only RCTs (7.8% difference). The effect was still present when haemodynamic responders were compared with non-responders. This analysis suggests a role of beta-blockers in preventing SBP in ascitic cirrhotics, independent of haemodynamic response. Further formal RCTs are needed to confirm this finding.

Circumferential 2D-strain imaging for the prediction of long term response to cardiac resynchronization therapy

BackgroundCardiac Resynchronization Therapy (CRT) leads to hemodynamic and clinical improvement in heart failure patients. The established methods to evaluate myocardial asynchrony analyze longitudinal and radial myocardial function. This study evaluates the new method of circumferential 2D-strain imaging in the prediction of the long-term response to CRT.Methods and results38 heart failure patients (NYHA II-III, QRS > 120 ms, LVEF < 0.35) received CRT and echocardiographic evaluation with a mean follow-up of 9.4 months. 18 (47.4%) of the patients were hemodynamic responders to long-term CRT. In the responder group, the maximum delay in the circumferential 2D-strain in the basal segments decreased (246 ± 94 to 123 ± 92 ms, p < 0.001). In the non-responder group there was no significant change (pre CRT: 195 ± 86, post CRT 135 ± 136 ms, p = 0.84). This was paralleled by a reduction of the maximum delay in the radial and longitudinal 2D strain in the basal segments. In ROC analysis, the baseline delay of circumferential 2D strain (AUC 0.66 (± 0.14)) does not predict a long-term response to CRT (p = 0.37).ConclusionThere is a significant decrease in the circumferential 2D-strain derived delays after CRT, indicating that resynchronization induces improvement in all three dimensions of myocardial contraction. However, the resulting predictive values of 2D strain delays are not superior to longitudinal and radial 2D-strain or TDI delays.