Lars Aaberge

Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris ☆: Clinical results from The Norwegian Randomized Trial

OBJECTIVES The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris. BACKGROUND Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published. METHODS One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2. RESULTS Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.) CONCLUSIONS Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.

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 .).

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.

Layer-Specific Quantification of Myocardial Deformation by Strain Echocardiography May Reveal Significant CAD in Patients With Non–ST-Segment Elevation Acute Coronary Syndrome

OBJECTIVES Our objective was to assess whether patients with significant coronary artery disease (CAD) had reduced endocardial function assessed by layer-specific strain compared with patients without significant CAD. BACKGROUND The left ventricular (LV) wall of the heart comprises 3 myocardial layers. The endocardial layer is most susceptible to ischemic injury. METHODS Seventy-seven patients referred to coronary angiography due to suspected non-ST-segment elevation-acute coronary syndromes (NSTE-ACS) were prospectively included. Coronary occlusion was found in 28, significant stenosis in 21, and no stenosis in 28 patients. Echocardiography was performed 1 to 2 h before angiography. Layer-specific longitudinal and circumferential strains were assessed from endocardium, mid-myocardium, and epicardium by 2-dimensional (2D) speckle-tracking echocardiography (STE). Territorial longitudinal strain (TLS) was calculated based on the perfusion territories of the 3 major coronary arteries in a 16-segment LV model, whereas global circumferential strain (GCS) was averaged from 6 circumferential LV segments in all 3 layers. RESULTS Patients with significant CAD had worse function in all 3 myocardial layers assessed by TLS and GCS compared with patients without significant CAD. Endocardial TLS (mean -14.0 ± 3.3% vs. -19.2 ± 2.2%; p < 0.001) and GCS (mean -19.3 ± 4.0% vs. -24.3 ± 3.4%; p < 0.001) were most affected. The absolute differences between endocardial and epicardial TLS and GCS were lower in patients with significant CAD (Δ2.4 ± 3.6% and Δ6.7 ± 3.8%, respectively) than in those without significant CAD (Δ5.3 ± 2.1% and Δ10.4 ± 3.0%; p < 0.001). This reflects a pronounced decrease in endocardial function in patients with significant CAD. A receiver-operating characteristic curve analysis showed that endocardial and mid-myocardial TLS were superior to identify significant CAD compared with epicardial TLS (p < 0.05), wall motion score index (p < 0.01), and ejection fraction (EF) (p < 0.001). CONCLUSIONS Assessment of layer-specific strain by 2D-STE might identify NSTE-ACS patients with significant CAD. Endocardial function was more affected in patients with significant CAD compared with epicardial function and EF.

Continued symptomatic improvement three to five years after transmyocardial revascularization with co2laser: A late clinical follow-up of the norwegian randomized trial with transmyocardial revascularization

Objectives The goals of this study were to assess late clinical outcome and left ventricular ejection fraction (LVEF) after transmyocardial revascularization with CO2laser (TMR). Background During the 1990s TMR emerged as a treatment option for patients with refractory angina not eligible for conventional revascularization. Few reports exist on clinical effects and LVEF >3 years after TMR. Methods One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized 1:1 to receive continued medical treatment or medical treatment combined with TMR. The patients were evaluated at baseline and after 3, 12 and 43 (range: 32 to 60) months with end points to angina, hospitalizations due to acute myocardial infarctions or unstable angina, heart failure and LVEF. Mortality was registered and MOS 36 Short-Form Health Survey answered at baseline and after 3, 6 and 12 months. Results Forty-three months after TMR, angina symptoms were still significantly improved, and unstable angina hospitalizations reduced by 55% (p < 0.001). Heart failure treatment (p < 0.01) increased, whereas the number of acute myocardial infarctions, LVEF and mortality was not affected. Quality of life was improved 3, 6 and 12 months after TMR. Conclusions Forty-three months after TMR, angina symptoms and hospitalizations due to unstable angina were significantly reduced, heart failure treatment increased and LVEF and mortality were seemingly unaffected.

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.

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.

Altered maternal left ventricular contractility and function during normal pregnancy.

To evaluate maternal left ventricular (LV) systolic and diastolic function during normal pregnancy by non‐invasive measures of LV contractility incorporating loading conditions.

Intra-aortic balloon counterpulsation as a bridge to heart transplantation does not impair long-term survival.

There are few studies of the use of intra‐aortic balloon pump (IABP) treatment as a bridge to heart transplantation (HTx). This is the first study to compare long‐term clinical and haemodynamic outcomes in IABP‐treated HTx patients and electively transplanted patients.

Duration of Myocardial Early Systolic Lengthening Predicts the Presence of Significant Coronary Artery Disease

OBJECTIVES This study sought to investigate whether the duration of left ventricular (LV) early systolic lengthening could accurately identify patients with significant coronary artery disease (CAD). BACKGROUND Ischemic myocardium with reduced active force will lengthen when LV pressure rises during early systole before onset of systolic shortening. METHODS We included 88 patients with suspected CAD referred to elective diagnostic coronary angiography. Two of these patients were excluded from the study due to evidence of previous myocardial infarction on contrast-enhanced magnetic resonance imaging. Speckle tracking echocardiography was performed before coronary angiography and at follow-up scheduled 1 year after revascularization, and global longitudinal strain and duration of average LV early systolic lengthening were recorded. RESULTS Forty-three of 86 patients had significant CAD. The duration of early systolic lengthening was significantly prolonged in patients with significant CAD compared with patients without significant coronary artery stenoses (76 ± 37 ms vs. 38 ± 23 ms, p < 0.001). Correspondingly, global systolic strain was significantly lower in patients with CAD (-17.7 ± 3.0% vs. -19.5 ± 2.6%, p = 0.003). Prolonged duration of early systolic lengthening showed the best accuracy in detecting CAD, with an area under the receiver-operating characteristic curve of 0.83. The area under the curve for global strain was 0.68. At 1-year follow-up, the duration of early systolic lengthening was significantly reduced (64 ± 37 ms vs. 76 ± 37 ms, p = 0.041) in the patients treated with revascularization. CONCLUSIONS Duration of myocardial early systolic lengthening was prolonged in patients with significant CAD; this might be a useful parameter to identify patients who might benefit from reperfusion therapy.