Trans-Cardiac Gradient of Secretoneurin in Patients with Takotsubo Syndrome.

INTRODUCTION: Secretoneurin (SN) is a novel biomarker that provides prognostic information in patients with cardiovascular disease. In experimental models, SN production is increased in the failing myocardium. Currently, no information is available on SN production in human myocardium. Accordingly, we wanted to determine the trans-cardiac gradient of SN in patients with Takotsubo syndrome (TTS), and to correlate circulating SN concentrations with indices of cardiac structure and function. METHODS: We included 15 women diagnosed with TTS according to established criteria. Plasma SN concentrations were measured in blood samples obtained simultaneously from the aortic root and the coronary sinus. Coronary physiology was assessed by invasive measurements, and we used cardiac magnetic resonance imaging to determine left ventricular ejection fraction (LVEF) and cardiac mass. RESULTS: Median age was 65 years and median LVEF was 45%. Median SN concentration was 39 (25th-75th percentile 31-44) pmol/L in the coronary sinus and 37 (30-41) pmol/L in the aortic root (p = 0.02 for difference). SN concentrations in the aortic root showed the highest correlations with N-terminal B-type natriuretic peptide (rho = 0.47) and estimated glomerular filtration rate (rho = -0.41). In contrast, we found weak correlations between SN concentrations and index of myocardial resistance (rho = 0.12), LVEF (rho = 0.08), and cardiac mass (rho = -0.09). CONCLUSION: We demonstrate a positive trans-cardiac gradient of SN in patients with TTS, which supports the hypothesis that SN is produced and released in the human myocardium in situations of myocardial dysfunction and stress.

An investigator-sponsored pragmatic randomized controlled trial of AntiCoagulation vs AcetylSalicylic Acid after Transcatheter Aortic Valve Implantation: Rationale and design of ACASA-TAVI.

BACKGROUND: The optimal antithrombotic therapy after transcatheter aortic valve implantation (TAVI) is unknown. Bioprosthetic valve dysfunction (BVD) is associated with adverse outcomes and may be prevented by anticoagulation therapy. A dedicated randomized trial comparing monotherapy NOAC to single antiplatelet therapy has not been performed previously. We hypothesize that therapy with any anti-factor Xa NOAC will reduce BVD compared to antiplatelet therapy, without compromising safety. METHODS: ACASA-TAVI is a multicenter, prospective, randomized, open-label, blinded endpoint, all-comers trial comparing a monotherapy anti-factor Xa NOAC strategy (intervention arm) with a single antiplatelet therapy strategy (control arm) after successful TAVI. Three-hundred and sixty patients without indication for oral anticoagulation will be randomized in a 1:1 ratio to either apixaban 5 mg twice per day, edoxaban 60 mg daily, or rivaroxaban 20 mg daily for 12 months followed by acetylsalicylic acid 75 mg daily indefinitely, or to acetylsalicylic acid 75 mg daily indefinitely. The 2 co-primary outcomes are (1) incidence of Hypo-Attenuated Leaflet Thickening (HALT) on 4-dimensional cardiac CT at 12 months, and (2) a Safety Composite of VARC-3 bleeding events, thromboembolic events (myocardial infarction and stroke), and death from any cause, at 12 months. RESULTS: The first 100 patients had a mean age of 74 ± 3.6 years, 33% were female, the average body-mass index was 27.9 ± 4.4 kg/m2, and 15% were smokers. A balloon-expanded valve was used in 82% and a self-expandable valve in 18%. CONCLUSIONS: The trial is planned, initiated, funded, and conducted without industry involvement. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05035277.

Exploring cardiac effects after oxytocin 2.5 IU or carbetocin 100 µg: A randomised controlled trial in women undergoing planned caesarean delivery.

BACKGROUND: Oxytocin can stimulate release of myocardial biomarkers troponin I and T, prolong QTc and induce ST-depression. OBJECTIVE: To explore cardiac changes after either intravenous carbetocin or oxytocin. STUDY DESIGN: Exploratory phase 4 randomised controlled trial. SETTING: Obstetrics units of Oslo University Hospital, Norway between September 2015 and May 2018. PARTICIPANTS: Forty healthy, singleton pregnant women aged 18 to 50 years at gestational age at least 36 weeks with a planned caesarean delivery. INTERVENTIONS: Participants were randomised to receive either oxytocin 2.5 IU or carbetocin 100 µg immediately after delivery. MAIN OUTCOME MEASURES: The primary endpoint was the assessment of troponin I within 48 h of study drug administration. Troponin I and T, and creatine kinase myocardial band assessments were measured before spinal anaesthesia (baseline), and again at 4, 10 and 24 h after delivery. QTc, ST-depression and relative increase in heart rate were recorded from start of study drug administration to 10 min after delivery. All adverse events were monitored. RESULTS: Compared with the carbetocin group, higher troponin I levels were observed in the oxytocin group at 4 h and 10 h after delivery. For both treatment groups, an increase from baseline in troponin I and T was most pronounced at 10 h after delivery, and it had begun to decline by 24 h. QTc increased with time after administration of both study drugs, with a mean maximum increase of 10.4 ms observed at 9 min (P   <  0.001). No statistical differences were observed in QTc ( P  = 0.13) or ST-depression ( P  = 0.11) between the treatment groups. CONCLUSIONS: Oxytocin 2.5 IU and carbetocin 100 µg caused a similar increase in QTc. The trial was underpowered with regards to ST-depression and the release of myocardial biomarkers and these warrant further investigation. Data from this trial will inform a larger phase 4 trial to determine potential drug differences in troponin release. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02528136.

Prognostic value of comprehensive intracoronary physiology assessment early after heart transplantation.

AIMS: We evaluated the long-term prognostic value of invasively assessing coronary physiology after heart transplantation in a large multicentre registry. METHODS AND RESULTS: Comprehensive intracoronary physiology assessment measuring fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) was performed in 254 patients at baseline (a median of 7.2 weeks) and in 240 patients at 1 year after transplantation (199 patients had both baseline and 1-year measurement). Patients were classified into those with normal physiology, reduced FFR (FFR ≤ 0.80), and microvascular dysfunction (either IMR ≥ 25 or CFR ≤ 2.0 with FFR > 0.80). The primary outcome was the composite of death or re-transplantation at 10 years. At baseline, 5.5% had reduced FFR; 36.6% had microvascular dysfunction. Baseline reduced FFR [adjusted hazard ratio (aHR) 2.33, 95% confidence interval (CI) 0.88-6.15; P = 0.088] and microvascular dysfunction (aHR 0.88, 95% CI 0.44-1.79; P = 0.73) were not predictors of death and re-transplantation at 10 years. At 1 year, 5.0% had reduced FFR; 23.8% had microvascular dysfunction. One-year reduced FFR (aHR 2.98, 95% CI 1.13-7.87; P = 0.028) and microvascular dysfunction (aHR 2.33, 95% CI 1.19-4.59; P = 0.015) were associated with significantly increased risk of death or re-transplantation at 10 years. Invasive measures of coronary physiology improved the prognostic performance of clinical variables (χ2 improvement: 7.41, P = 0.006). However, intravascular ultrasound-derived changes in maximal intimal thickness were not predictive of outcomes. CONCLUSION: Abnormal coronary physiology 1 year after heart transplantation was common and was a significant predictor of death or re-transplantation at 10 years.

Safety and feasibility of dobutamine stress echocardiography in symptomatic high gradient aortic stenosis patients scheduled for transcatheter aortic valve implantation.

PURPOSE: We aimed to study the safety and feasibility of low-dose dobutamine stress echocardiography in a symptomatic high gradient aortic stenosis population scheduled for transfemoral transcatheter aortic valve implantation (TAVI) and to quantify left ventricular (LV) flow reserve. METHODS: Fifty patients underwent dobutamine stress echocardiography with 5 minutes increments of 5 µg/kg/min up to 20 µg/kg/min until the heart rate increased ≥20 beats/min from baseline or exceeded 100 beats/min. Other criteria for discontinuing the infusion were major adverse events: ventricular arrhythmia, persistent supraventricular arrhythmia, pulmonary edema, chest pain with significant ST-changes, or minor events: ST-changes, drop in systolic blood pressure >30 mmHg, mild chest pain, and/or dyspnea. LV flow reserve was defined as an increase in stroke volume ≥20% during the test. RESULTS: Of 50 patients, 45 completed the test according to protocol. No patient had major adverse event. Five patients experienced minor side effects: mild chest pain/dyspnea in three, self-terminating atrial flutter in one, and decrease in blood pressure in one. Significant LV flow reserve was observed in 20 patients (40%). CONCLUSION: Low-dose dobutamine stress test appeared safe and feasible patients with high gradient aortic stenosis, and showed LV flow reserve in a minority of them.

Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease.

BACKGROUND: Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. METHODS: We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. RESULTS: At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. CONCLUSIONS: In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double-blind randomized study.

INTRODUCTION: Many women undergoing coronary angiography for chest pain have no or only minimal coronary artery disease (CAD). However, despite the lack of obstructive CAD, they still have an increased risk of major adverse cardiovascular events. Pleiotropic effects of statins may influence microvascular function, but if statins improve microvascular function in unselected chest pain patients is not well studied. This study assessed microvascular function by using the thermodilution-derived test "the index of microvascular resistance" (IMR) with the aim of determining the (i) IMR level in women with chest pain and non-obstructive CAD and if (ii) IMR is modified by high-dose statin treatment in these patients. Additional objectives were to identify the influence of statins on the health status as assessed with generic health questionnaires and on biomarkers of endothelial activation. MATERIALS AND METHODS: The study was a randomized, double-blind, single-center trial comparing 6 months of rosuvastatin treatment with placebo. In total, 66 women without obstructive CAD were included. Mean age was 52.7 years and 55.5 years in the placebo and rosuvastatin group, respectively. Microvascular function was assessed using the IMR, health status was assessed using the SF-36 and EQ-5D questionnaires, and biochemical values were assessed at baseline and 6 months later. RESULTS AND CONCLUSIONS: In the placebo group IMR was 14.6 (SD 5.7) at baseline and 14.4 (SD 6.5) at follow-up. In the rosuvastatin group IMR was 16.5 (SD 7.5) at baseline and 14.2 (SD 5.8) at follow-up. IMR did not differ significantly between the two study groups at follow-up controlled for preintervention values. C-reactive protein (CRP) was comparable between the groups at baseline, while at follow-up CRP was significantly lower in the rosuvastatin group compared to placebo [0.6 (±0.5) mg/L vs. 2.6 (±3.0) mg/L; p = 0.002]. Whereas rosuvastatin treatment for 6 months attenuated CRP levels, it did not improve microvascular function as assessed by IMR (Clinical Trials.gov NCT01582165, EUDRACT 2011-002630-39.3tcAZ).

Intra-aortic balloon pump in acute chest pain and cardiogenic shock - a long-term follow-up.

Objectives. Coronary revascularisation and intra-aortic balloon pump (IABP) has been considered the gold standard treatment of acute coronary syndrome with cardiogenic shock, recently challenged by the SHOCK II study. The aim of this non-randomised study was to investigate the long term prognosis after immediate IABP supported angiography, in patients with acute chest pain and cardiogenic shock, treated with percutaneous coronary intervention (PCI), cardiac surgery or optimal medical treatment. We assessed data from 281 consecutive patients admitted to our department from 2004 to 2010. Results. Mean (±SD) age was 63.8 ± 11.5 (range 30-84) years with a follow-up of 5.6 ± 4.4 (0-12.7) years. Acute myocardial infarction was the primary diagnosis in 93% of the patients, 4% presented with unstable angina pectoris and 3% cardiomyopathy or arrhythmias of non-ischemic aetiology. Systolic blood pressure at admittance was 85 ± 18 mmHg and diastolic 55 ± 18 mmHg. Thirty day, one- and five-year survival was 71.2%, 67.3% and 57.7%, respectively. PCI was performed immediately in 70%, surgery was done in 17%, and 13% were not eligible for any revascularisation. Independent variables predicting mortality were medical treatment vs revascularisation, out-of-hospital cardiac arrest, and advanced age. Three serious non-fatal complications occurred due to IABP treatment, i.e. 0.001 per treatment day. Conclusions. We report the use of IABP in patients with acute chest pain admitted for angiography. Long-term survival is acceptable and discriminating factors were no revascularisation, out-of-hospital cardiac arrest and age. IABP was safe and feasible and the complication rate was low.

The predictive value of coronary artery calcium detected by computed tomography in a prospective study on cardiac allograft vasculopathy in heart transplant patients.

The predictive value of coronary artery calcium (CAC) in heart transplant (HTX) patients is not established. We explored if the absence of CAC on computed tomography (CT) could exclude moderate and severe cardiac allograft vasculopathy [CAV2-3 ; the International Society for Heart and Lung Transplantation (ISHLT) recommended nomenclature] and significant coronary artery stenosis (diameter reduction ≥50%) and predict long-term clinical outcomes. HTX recipients (n = 133) were prospectively included and underwent CT for CAC scoring and invasive coronary angiography (ICA) 7.8 ± 5.0 years after HTX. CAC was detected in 73 (55%) patients. The absence of CAC on CT had a negative predictive value of 97% for ISHLT CAV2-3 and 88% for significant stenosis on ICA. During 7.5 ± 2.6 years of follow-up after CAC CT (n = 127), there were 57 (45%) nonfatal major adverse cardiac events and 23 (18%) deaths or graft losses registered as first events. Patients with CAC had significantly more events (P = 0.011). In an adjusted Cox regression analysis, the presence of CAC was significantly associated with a negative outcome (HR 1.8, 95% CI 1.1-3.0; P = 0.023). The absence of CAC predicted low prevalences of ISHLT CAV2-3 and significant coronary artery stenosis in HTX patients. The presence of CACS was significantly associated with a worse long-term outcome.

Health-related quality of life in older patients with acute coronary syndrome randomised to an invasive or conservative strategy. The After Eighty randomised controlled trial.

Objective: in the After Eighty study (ClinicalTrials.gov.number, NCT01255540), patients aged 80 years or more, with non-ST-elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UAP), were randomised to either an invasive or conservative management approach. We sought to compare the effects of these management strategies on health related quality of life (HRQOL) after 1 year. Methods: the After Eighty study was a prospective randomised controlled multicenter trial. In total, 457 patients aged 80 or over, with NSTEMI or UAP, were randomised to either an invasive strategy (n = 229, mean age: 84.7 years), involving early coronary angiography, with immediate evaluation for percutaneous coronary intervention, coronary artery bypass graft, optimal medical therapy, or to a conservative strategy (n = 228, mean age: 84.9 years). The Short Form 36 health survey (SF-36) was used to assess HRQOL at baseline, and at the 1-year follow-up. Results: baseline SF-36 completion was achieved for 208 and 216 patients in the invasive and conservative groups, respectively. A total of 137 in the invasive group and 136 patients in the conservative group completed the SF-36 form at follow-up. When comparing the changes from follow-up to baseline (delta) no significant changes in quality-of-life scores were observed between the two strategies in any of the domains, expect for a small but statistically significant difference in bodily pain. This difference in only one of the SF-36 subscales may not necessarily be clinically significant. Conclusion: from baseline to the 1 year follow-up, only minor differences in change of HRQOL as measured by SF-36 were seen by comparing an invasive and conservative strategy. ClinicalTrials.gov identifier: NCT01255540.

Coronary computed tomography in heart transplant patients: detection of significant stenosis and cardiac allograft vasculopathy, image quality, and radiation dose.

Background Cardiac allograft vasculopathy (CAV) is an accelerated form of atherosclerosis unique to heart transplant (HTX) patients. Purpose To investigate the detection of significant coronary artery stenosis and CAV, determinants of image quality, and the radiation dose in coronary computed tomography angiography (CCTA) of HTX patients with 64-slice multidetector CT (64-MDCT). Material and Methods Fifty-two HTX recipients scheduled for invasive coronary angiography (ICA) were prospectively enrolled and underwent CCTA before ICA with intravascular ultrasound (IVUS). Results Interpretable CCTA images were acquired in 570 (95%) coronary artery segments ≥2 mm in diameter. Sensitivity, specificity, and positive and negative predictive values of CCTA for the detection of segments with significant stenosis (lumen reduction ≥50%) on ICA were 100%, 98%, 7.7%, and 100%, respectively. Twelve significant stenoses were located in segments with uninterpretable image quality or vessel diameter <2 mm; only one was eligible for intervention. IVUS detected CAV (maximal intimal thickness ≥0.5 mm) in 33/41 (81%) patients; CCTA and ICA identified CAV (any wall or luminal irregularity) in 18 (44%) and 14 (34%) of these 33 patients, respectively. The mean estimated radiation dose was 19.0 ± 3.4 mSv for CCTA and 5.7 ± 3.3 mSv for ICA ( P < 0.001). Conclusion CCTA with interpretable image quality had a high negative predictive value for ruling out significant stenoses suitable for intervention. The modest detection of CAV by CCTA implied a limited value in identifying subtle CAV. The high estimated radiation dose for 64-MDCT is of concern considering the need for repetitive examinations in the HTX population.

Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial.

BACKGROUND: Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy. METHODS: In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used. This study is registered with ClinicalTrials.gov, number NCT01255540. FINDINGS: During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41-0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35-0·76; p=0·0010) for myocardial infarction, 0·19 (0·07-0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25-1·46; p=0·2650) for stroke, and 0·89 (0·62-1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications. INTERPRETATION: In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications. FUNDING: Norwegian Health Association (ExtraStiftelsen) and Inger and John Fredriksen Heart Foundation.

Comparison of simplified and comprehensive methods for assessing the index of microvascular resistance in heart transplant recipients.

OBJECTIVES: The objectives of the present study were to compare a simplified and a comprehensive method of estimating the index of microvascular resistance (IMR) and assess the changes from 7-11 weeks to 1 year after heart transplant (HTx). BACKGROUND: he IMR is specific to the microvasculature and reflects the status of the microcirculation in cardiac patients and can be estimated via a simplified method (IMR(s)) or a comprehensive method (IMR(c)). The calculation for the latter includes coronary wedge pressure and central venous pressure. METHODS: Consecutively transplanted patients (n = 48) underwent left and right heart catheterization including physiological evaluation at two time points post-HTx. The agreement between the values of IMR obtained using the IMR(s) and IMR(c) methods were assessed using Bland-Altman analysis. The agreements and differences were assessed using mixed model analysis. RESULTS: The mean bias between IMRs and IMRc was 1.3 mm Hg·s (95% limits of agreement: -1.2, 3.8 mm Hg). Between 7-11 weeks and 1 year post-HTx there was a significant decline in IMR(s) values (P = 0.03) but a smaller and statistically nonsignificant decline in IMR(c) values (P = 0.13). The significant difference (P = 0.04) between IMR(c) and IMR(s) 7-11 weeks post-HTx was no longer present at 1 year (P = 0.24). CONCLUSIONS: The IMR(s) method resulted in slightly higher IMR estimates and exhibited a somewhat larger change over the 10-month follow-up period than the IMR(c) method. However, the differences between the methods were small and unlikely to be of clinical importance.

Left ventricular mechanical dispersion as a predictor of the need for pacemaker implantation after transcatheter aortic valve implantation: MeDiPace TAVI study.

AIMS: Permanent pacemaker (PM) implantation is common after transcatheter aortic valve implantation (TAVI). Left ventricular mechanical dispersion (MeDi) by speckle tracking echocardiography is a marker of fibrosis that causes alterations in the conduction system. We hypothesized that MeDi can be a predictor of the need for PM implantation after TAVI. METHODS AND RESULTS: Consecutively, 200 TAVI patients were enrolled. Transthoracic echocardiography and electrocardiography examinations were recorded before TAVI to evaluate global longitudinal strain (GLS), MeDi, and conduction disturbances. PM implantation information was obtained 3 months after TAVI. Patients were stratified into PM or no PM group. Mean age was 80 + 7 years (44% women). Twenty-nine patients (16%) received PM. MeDi, QRS duration, existence of right bundle branch abnormality (RBBB), and first-degree atrioventricular (AV) block were significantly different between groups. MeDi was 57 ± 15 ms and 48 ± 12 ms in PM and no PM groups, respectively (P < 0.001). In multivariate analysis, MeDi predicted the need for PM after TAVI independently of GLS, QRS duration, RBBB, and first-degree AV block [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.22-2.45] with an area under the curve (AUC) of 0.68 in receiver operating characteristic (ROC) curves. Moreover, RBBB was an independent predictor of PM need after TAVI (OR: 8.98, 95% CI: 1.78-45.03). When added to RBBB, MeDi had an incremental predictive value with an AUC of 0.73 in ROC curves (P = 0.01). CONCLUSION: MeDi may be used as an echocardiographic functional predictor of the need for PM after TAVI.

Assessment of wasted myocardial work: a novel method to quantify energy loss due to uncoordinated left ventricular contractions.

Left ventricular (LV) dyssynchrony reduces myocardial efficiency because work performed by one segment is wasted by stretching other segments. In the present study, we introduce a novel noninvasive clinical method that quantifies wasted energy as the ratio between work consumed during segmental lengthening (wasted work) divided by work during segmental shortening. The wasted work ratio (WWR) principle was studied in 6 anesthetized dogs with left bundle branch block (LBBB) and in 28 patients with cardiomyopathy, including 12 patients with LBBB and 10 patients with cardiac resynchronization therapy. Twenty healthy individuals served as controls. Myocardial strain was measured by speckle tracking echocardiography, and LV pressure (LVP) was measured by micromanometer and a previously validated noninvasive method. Segmental work was calculated by multiplying strain rate and LVP to get instantaneous power, which was integrated to give work as a function of time. A global WWR was also calculated. In dogs, WWR by estimated LVP and strain showed a strong correlation (r = 0.94) and good agreement with WWR by the LV micromanometer and myocardial segment length by sonomicrometry. In patients, noninvasive WWR showed a strong correlation (r = 0.96) and good agreement with WWR using the LV micromanometer. Global WWR was 0.09 ± 0.03 in healthy control subjects, 0.36 ± 0.16 in patients with LBBB, and 0.21 ± 0.09 in cardiomyopathy patients without LBBB. Cardiac resynchronization therapy reduced global WWR from 0.36 ± 0.16 to 0.17 ± 0.07 (P < 0.001). In conclusion, energy loss due to incoordinated contractions can be quantified noninvasively as the LV WWR. This method may be applied to evaluate the mechanical impact of dyssynchrony.

Sensitive troponin assays and N-terminal pro-B-type natriuretic peptide in acute coronary syndrome: prediction of significant coronary lesions and long-term prognosis.

BACKGROUND: Sensitive troponin assays have substantially improved early diagnosis of myocardial infarction. However, the role of sensitive cardiac troponin (cTn) assays in prediction of significant coronary lesions and long-term prognosis in non-ST-elevation acute coronary syndrome (NSTE-ACS) remains unresolved. METHODS: This prospective study includes 458 consecutive patients with NSTE-ACS admitted for coronary angiography. Serum levels of 4 commercial available sensitive troponin assays were analyzed (Roche high-sensitive cTnT [hs-cTnT; Roche Diagnostics, Basel, Switzerland], Siemens cTnI Ultra [Siemens, Munich, Germany], Abbott-Architect cTnI [Abbott, Abbott Park, IL], Access Accu-cTnI [Beckman Coulter, Nyon, Switzerland]), as well as a standard assay (Roche cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), before coronary angiography. RESULTS: The relationship between the analyzed biomarkers and significant coronary lesions on coronary angiography, as quantified by area under the receiver operating characteristic curve, was significantly higher with Roche hs-cTnT, Siemens cTnI Ultra, and Access Accu-cTnI as compared with standard troponin T assay (P < .001 for all comparisons). This difference was mainly caused by increased sensitivity below the 99th percentile. Also, NT-proBNP was associated with the presence of significant coronary lesions. Cardiac troponin values were correlated with cardiac death (primary end point) during 1373 (1257-1478) days of follow-up. In both univariate and multivariate Cox regression analyses, NT-proBNP was superior to both hs-cTnT and cTnI in prediction of cardiovascular mortality. Troponin values with all assays were correlated with the need for repeated revascularization (secondary end point) during follow-up. CONCLUSIONS: Sensitive cTn assays are superior to standard cTnT assay in prediction of significant coronary lesions in patients with NSTE-ACS. However, this improvement is primary caused by increased sensitivity below the 99th percentile. N-terminal pro-B-type natriuretic peptide is superior to cTns in prediction of long-term mortality.

A novel clinical method for quantification of regional left ventricular pressure-strain loop area: a non-invasive index of myocardial work.

AIMS: Left ventricular (LV) pressure-strain loop area reflects regional myocardial work and metabolic demand, but the clinical use of this index is limited by the need for invasive pressure. In this study, we introduce a non-invasive method to measure LV pressure-strain loop area. METHODS AND RESULTS: Left ventricular pressure was estimated by utilizing the profile of an empiric, normalized reference curve which was adjusted according to the duration of LV isovolumic and ejection phases, as defined by timing of aortic and mitral valve events by echocardiography. Absolute LV systolic pressure was set equal to arterial pressure measured invasively in dogs (n = 12) and non-invasively in patients (n = 18). In six patients, myocardial glucose metabolism was measured by positron emission tomography (PET). First, we studied anaesthetized dogs and observed an excellent correlation (r = 0.96) and a good agreement between estimated LV pressure-strain loop area and loop area by LV micromanometer and sonomicrometry. Secondly, we validated the method in patients with various cardiac disorders, including LV dyssynchrony, and confirmed an excellent correlation (r = 0.99) and a good agreement between pressure-strain loop areas using non-invasive and invasive LV pressure. Non-invasive pressure-strain loop area reflected work when incorporating changes in local LV geometry (r = 0.97) and showed a strong correlation with regional myocardial glucose metabolism by PET (r = 0.81). CONCLUSIONS: The novel non-invasive method for regional LV pressure-strain loop area corresponded well with invasive measurements and with directly measured myocardial work and it reflected myocardial metabolism. This method for assessment of regional work may be of clinical interest for several patients groups, including LV dyssynchrony and ischaemia.