OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

BACKGROUND: Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS: We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS: We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P = 0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group. CONCLUSIONS: Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Extended Follow-Up of a 2×2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol.

BACKGROUND: Adjuvant breast cancer therapy containing anthracyclines with or without anti-human epidermal growth factor receptor-2 antibodies and radiotherapy is associated with cancer treatment-related cardiac dysfunction. In the PRADA trial (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy), concomitant treatment with the angiotensin receptor blocker candesartan attenuated the reduction in left ventricular ejection fraction (LVEF) in women receiving treatment for breast cancer, whereas the ß-blocker metoprolol attenuated the increase in cardiac troponins. This study aimed to assess the long-term effects of candesartan and metoprolol or their combination to prevent a reduction in cardiac function and myocardial injury. METHODS: In this 2×2 factorial, randomized, placebo-controlled, double-blind, single-center trial, patients with early breast cancer were assigned to concomitant treatment with candesartan cilexetil, metoprolol succinate, or matching placebos. Target doses were 32 and 100 mg, respectively. Study drugs were discontinued after adjuvant therapy. All 120 validly randomized patients were included in the intention-to-treat analysis. The primary outcome measure was change in LVEF assessed by cardiovascular magnetic resonance imaging from baseline to extended follow-up. Secondary outcome measures included changes in left ventricular volumes, echocardiographic peak global longitudinal strain, and circulating cardiac troponin concentrations. RESULTS: A small decline in LVEF but no significant between-group differences were observed from baseline to extended follow-up, at a median of 23 months (interquartile range, 21 to 28 months) after randomization (candesartan, 1.7% [95% CI, 0.5 to 2.8]; no candesartan, 1.8% [95% CI, 0.6 to 3.0]; metoprolol, 1.6% [95% CI, 0.4 to 2.7]; no metoprolol, 1.9% [95% CI, 0.7 to 3.0]). Candesartan treatment during adjuvant therapy was associated with a significant reduction in left ventricular end-diastolic volume compared with the noncandesartan group (P=0.021) and attenuated decline in global longitudinal strain (P=0.046) at 2 years. No between-group differences in change in cardiac troponin I and T concentrations were observed. CONCLUSIONS: Anthracycline-containing adjuvant therapy for early breast cancer was associated with a decline in LVEF during extended follow-up. Candesartan during adjuvant therapy did not prevent reduction in LVEF at 2 years, but was associated with modest reduction in left ventricular end-diastolic volume and preserved global longitudinal strain. These results suggest that a broadly administered cardioprotective approach may not be required in most patients with early breast cancer without preexisting cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01434134.

Gene expression of fibrinolytic markers in coronary thrombi.

BACKGROUND: The fibrinolytic system plays an important role in coronary artery atherothrombosis, and especially circulating plasminogen-activator inhibitor (PAI) type 1 (PAI-1) associates with increased mortality, infarct size and heart failure in patients with myocardial infarction (MI). In a cross-sectional study, we aimed to study whether genes encoding tissue plasminogen activator (tPA), urinary-type plasminogen activator (uPA), PAI-1 and PAI-2 are expressed in coronary thrombi from acute ST-elevation MI (STEMI) patients. Any relations to myocardial injury measured by peak troponin T, time from symptom onset to Percutaneous Coronary Intervention (PCI), and to different cell types present in the thrombi were also explored. METHODS: Intracoronary thrombi were aspirated from 33 STEMI patients treated with primary PCI. The thrombi were snap-frozen for gene expression analyses, relatively quantified by RT PCR. Peripheral blood samples were drawn. Correlations were performed by Spearmans rho. RESULTS: The genes were present in 74-94% of the thrombi. Median peak troponin T was 3434 µ/L and median ischemic time 152 min. There were no significant correlations between the measured genes and troponin T, or ischemic time. Genes encoding tPA, u-PA, PAI-1 and PAI-2 all correlated significantly to the presence of monocytes/macrophages (CD68) in the thrombi (p = 0.028, p < 0.001, p = 0.003, p < 0.001). PAI-1 and PAI-2 also correlated to endothelial cells (CD31) (p = 0.002, p = 0.016). uPA associated with neutrophil granulocytes (CD 66b) (p = 0.019). CONCLUSION: Genes encoding tPA, uPA, PAI-1 and PAI-2 were highly expressed in human coronary thrombi from STEMI patients, indicating fibrinolytic regulators playing active roles in the thrombi, although not related to myocardial injury. All markers related to the presence of monocytes/macrophages, indicating connection to local inflammatory cells. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov with identification number NCT02746822 .

Renal sympathetic denervation lowers systemic vascular resistance in true treatment-resistant hypertension.

PURPOSE: Renal sympathetic denervation (RDN) is again gaining interest as recent well-designed trials have demonstrated reduced ambulatory blood pressure (BP) after RDN. However, the hemodynamic mechanisms have not been elucidated. We aimed for the first time to investigate the effect of RDN on the "Hallmark of Hypertension" namely increased systemic vascular resistance index (SVRI). MATERIALS AND METHODS: We investigated SVRI change in patients with true treatment-resistant hypertension randomised to RDN (n = 9) or drug adjusted control (n = 9). Treatment-resistant hypertension was defined as office systolic BP ≥ 140 mmHg despite ≥ 3 antihypertensive drugs including a diuretic. True treatment-resistant hypertension was confirmed prior to inclusion with ambulatory daytime systolic BP ≥ 135 mmHg immediately after witnessed intake of antihypertensive drugs. Hemodynamic variables were recorded with thoracic impedance cardiography at baseline and at three and six months follow-up after RDN. This non-invasive method also guided further tailoring of drug treatment in the control group aiming to normalise hemodynamic variables and BP. RESULTS: From three to six months follow-up after RDN, SVRI decreased with a median of -611 dyn*s*m2/cm5 [IQR -949 to -267] (p < 0.01), while supine mean BP decreased with a median of -11 mmHg [IQR -21 to -3] (p = 0.02). In the same period, SVRI in the control group was reduced with -674 dyn*s*m2/cm5 [IQR -1,309 to -340] (p < 0.01), while supine mean BP decreased with -15 mmHg [IQR -29 to -6] (p = 0.01). Thus, hemodynamic variables and BP in the two groups normalised in parallel. CONCLUSION: Our data suggest that in patients with true treatment-resistant hypertension, renal sympathetic denervation lowers BP by reducing systemic vascular resistance of similar size as in the control group with careful individual selection of antihypertensive drugs and dose titration.

Safety and efficacy of hybrid vascular closure technique using both a suture- and collagen-mediated closure device after transfemoral transcatheter aortic valve implantation.

OBJECTIVES: To evaluate the clinical utility and feasibility of a hybrid technique for obtaining vascular hemostasis by combining a suture- and a collagen-mediated system after transfemoral transcatheter aortic valve implantation (TF TAVI) in a real-world setting. METHODS: In 75 consecutive TF TAVI procedures, we investigated a hybrid closing method to achieve hemostasis at the large bore puncture site using a combination of one presuture closure system (ProGlide) and one collagen-mediated system (Angio-Seal). Vascular complications at puncture site were recorded until discharge. RESULTS: Successful hemostasis by the hybrid technique was achieved in 74 out of 75 patients, and the method was well tolerated by all patients. In 73 patients, (97.3%) neither puncture site related complications nor serious early or late bleedings were observed during a median hospital stay of 2 days postprocedure. CONCLUSION: This single-center registry study indicates that a percutaneous hybrid closure technique is safe and efficacious in closing large bore arteriotomies. It is an easy and reliable technique that may contribute to simplifying TAVI procedures. STUDY REGISTRATION: The data was collected from an internal quality control registry on treatment of patients with valvular heart disease with or without coronary artery disease, No 2014/17280, Oslo University Hospital, Ullevål.

Microvascular perfusion in infarcted and remote myocardium after successful primary PCI: angiographic and CMR findings.

OBJECTIVES: The aim of this study was to investigate the association between TIMI myocardial perfusion (TMP) grading acute and cardiac magnetic resonance (CMR) first-pass perfusion early and at 4 months in patients with ST-segment-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). MATERIAL AND METHODS: One hundred ninety-eight STEMI patients were recruited from the POSTEMI study. TMP grade was assessed after PCI; CMR was performed at day 2 and after 4 months. Signal intensity was measured on first-pass perfusion images, and a maximum contrast enhancement index (MCE) was calculated. RESULTS: Patients with TMP grade 2-3 (n = 108) after PCI had significantly better EF (59 ± 10 vs. 51 ± 13, p < 0.001) and smaller infarct volume (12 ± 8 vs. 19 ± 12 %, p < 0.001) at 4 months compared with patients with TMP grade 0-1 (n = 81). MCE in the infarcted (MCEi) and remote myocardium (MCEr) improved from early to follow-up CMR, MCEi from 94 ± 56 to 126 ± 59, p < 0.001, and MCEr from 112 ± 51 to 127 ± 50, p < 0.001. In patients with the lowest CMR perfusion early, perfusion at 4 months remained decreased compared with the other groups, MCEi 108 ± 75 vs. 133 ± 51, p = 0.01, and MCEr 115 ± 41 vs. 131 ± 52, p = 0.047. CONCLUSION: TMP grade and early CMR first-pass perfusion were associated with CMR outcomes at 4 months. First-pass perfusion improved after 4 months in the infarcted and remote myocardium. However, in patients with the lowest CMR perfusion early, perfusion was still reduced after 4 months. KEY POINTS: • Cardiac magnetic resonance myocardial first-pass perfusion and TMP grading after successful PCI helps to assess risk in patients with ST elevation myocardial infarction. • Cardiac magnetic resonance myocardial first-pass perfusion shows that microvascular perfusion after ST elevation myocardial infarction can be impaired in both infarcted and non-infarcted myocardium. • Microvascular perfusion improves over time in patients with ST elevation myocardial infarction treated with primary PCI.

Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI.

BACKGROUND: The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. METHODS AND RESULTS: In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p ≤ 0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p < 0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p ≤ 0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p < 0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p = 0.012). No such observations were encountered for MPO-DNA. CONCLUSIONS: High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008)).

Renal artery and parenchymal changes after renal denervation: assessment by magnetic resonance angiography.

OBJECTIVES: Relatively little is known about the incidence of long-term renal damage after renal denervation (RDN), a potential new treatment for hypertension. In this study the incidence of renal artery and parenchymal changes, assessed with contrast-enhanced magnetic resonance angiography (MRA) after RDN, is investigated. METHODS: This study is an initiative of ENCOReD, a collaboration of hypertension expert centres. Patients in whom an MRA was performed before and after RDN were included. Scans were evaluated by two independent, blinded radiologists. Primary outcome was the change in renal artery morphology and parenchyma. RESULTS: MRAs from 96 patients were analysed. Before RDN, 41 renal anomalies were observed, of which 29 mostly mild renal artery stenoses. After a median time of 366 days post RDN, MRA showed a new stenosis (25-49% lumen reduction) in two patients and progression of pre-existing lumen reduction in a single patient. No other renal changes were observed and renal function remained stable. CONCLUSIONS: We observed new or progressed renal artery stenosis in three out of 96 patients, after a median time of 12 months post RDN (3.1%). Procedural angiographies showed that ablations were applied near the observed stenosis in only one of the three patients. KEY POINTS: • The incidence of vascular changes 12 months post RDN was 3.1%. • No renal vascular or parenchymal changes other than stenoses were observed. • Ablations were applied near the stenosis in only one of three patients.

Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol.

AIMS: Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the ß-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. METHODS AND RESULTS: In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the ß-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI -0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. CONCLUSION: In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function.

A new automatic algorithm for quantification of myocardial infarction imaged by late gadolinium enhancement cardiovascular magnetic resonance: experimental validation and comparison to expert delineations in multi-center, multi-vendor patient data.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) using magnitude inversion recovery (IR) or phase sensitive inversion recovery (PSIR) has become clinical standard for assessment of myocardial infarction (MI). However, there is no clinical standard for quantification of MI even though multiple methods have been proposed. Simple thresholds have yielded varying results and advanced algorithms have only been validated in single center studies. Therefore, the aim of this study was to develop an automatic algorithm for MI quantification in IR and PSIR LGE images and to validate the new algorithm experimentally and compare it to expert delineations in multi-center, multi-vendor patient data. METHODS: The new automatic algorithm, EWA (Expectation Maximization, weighted intensity, a priori information), was implemented using an intensity threshold by Expectation Maximization (EM) and a weighted summation to account for partial volume effects. The EWA algorithm was validated in-vivo against triphenyltetrazolium-chloride (TTC) staining (n = 7 pigs with paired IR and PSIR images) and against ex-vivo high resolution T1-weighted images (n = 23 IR and n = 13 PSIR images). The EWA algorithm was also compared to expert delineation in 124 patients from multi-center, multi-vendor clinical trials 2-6 days following first time ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) (n = 124 IR and n = 49 PSIR images). RESULTS: Infarct size by the EWA algorithm in vivo in pigs showed a bias to ex-vivo TTC of -1 ± 4%LVM (R = 0.84) in IR and -2 ± 3%LVM (R = 0.92) in PSIR images and a bias to ex-vivo T1-weighted images of 0 ± 4%LVM (R = 0.94) in IR and 0 ± 5%LVM (R = 0.79) in PSIR images. In multi-center patient studies, infarct size by the EWA algorithm showed a bias to expert delineation of -2 ± 6 %LVM (R = 0.81) in IR images (n = 124) and 0 ± 5%LVM (R = 0.89) in PSIR images (n = 49). CONCLUSIONS: The EWA algorithm was validated experimentally and in patient data with a low bias in both IR and PSIR LGE images. Thus, the use of EM and a weighted intensity as in the EWA algorithm, may serve as a clinical standard for the quantification of myocardial infarction in LGE CMR images. CLINICAL TRIAL REGISTRATION: CHILL-MI: NCT01379261 . MITOCARE: NCT01374321 .

Fractalkine levels are elevated early after PCI-treated ST-elevation myocardial infarction; no influence of autologous bone marrow derived stem cell injection.

BACKGROUND: Fractalkine (CX3CL1) is a chemokine associated with atherosclerosis and inflammation. There is limited knowledge of fractalkine levels during acute myocardial infarction (AMI) and stem cell treatment. We aimed to investigate the time profile of circulating fractalkine and gene expression of its receptor CX3CR1 during AMI, and the influence of intracoronary autologous bone marrow stem cell (mBMC) transplantation (given 6 days after AMI) on fractalkine levels. METHODS: We examined fractalkine levels at different time points by enzyme-linked immunosorbent assay (ELISA) in 20 patients with AMI, and 10 patients with stable angina pectoris (AP) undergoing percutaneous coronary intervention (PCI), and in 100 patients included in the randomized Autologous Stem-Cell Transplantation in Acute Myocardial Infarction (ASTAMI) trial. RESULTS: Patients with AMI had significantly elevated levels 3- and 12 h after PCI compared to patients with stable AP. After 12 h levels were similar in the two groups. An inverse pattern was observed in gene expression levels. No correlation between fractalkine levels and myocardial injury or infarct size was seen. We could not demonstrate any influence of autologous mBMC transplantation on fractalkine levels. CONCLUSION: Fractalkine levels are elevated the first 12 h after PCI in patients with AMI, however, not correlated to infarct size. The inverse pattern in gene expression of fractalkine receptor (CX3CR1) might be a compensatory mechanism. No effect of autologous mBMC transplantation given 6 days after AMI on fractalkine levels was observed.

The time profile of Pentraxin 3 in patients with acute ST-elevation myocardial infarction and stable angina pectoris undergoing percutaneous coronary intervention.

BACKGROUND: High levels of Pentraxin 3 (PTX3) are reported in acute myocardial infarction (AMI). AIM: To investigate circulating levels and gene expression of PTX3 in patients with AMI and stable angina pectoris (AP) undergoing PCI. METHODS: Ten patients with AP and 20 patients with AMI were included. Blood samples were drawn before PCI in the AP group and after 3 and 12 hours and days 1, 3, 5, 7, and 14 in both groups. RESULTS: Circulating PTX3 levels were higher in AMI compared to AP at 3 and 12 hours (P < 0.001 and P = 0.003). Within the AMI group, reduction from 3 hours to all later time points was observed (all P ≤ 0.001). Within the AP group, increase from baseline to 3 hours (P = 0.022), followed by reductions thereafter (all P < 0.05), was observed. PTX3 mRNA increased in the AMI group from 3 hours to days 7 and 14 in a relative manner of 62% and 73%, while a relative reduction from baseline to 3 and 12 hours of 29% and 37% was seen in the AP group. CONCLUSION: High circulating PTX3 levels shortly after PCI in AMI indicate that AMI itself influences PTX3 levels. PTX3 mRNA might be in response to fluctuations in circulating levels.

[Renal sympathetic denervation in treatment-resistant hypertension]. / Renal sympatisk denervering ved terapiresistent hypertensjon.

BACKGROUND: Renal denervation (RDN) has been introduced as a potential new treatment for patients with treatment-resistant hypertension, defined as a blood pressure above 140/90 mm Hg despite treatment with at least three antihypertensive drugs. We present an overview of this type of treatment, describe the method and discuss its possible future uses. METHOD: The review is based on a discretionary selection of relevant articles from our archive, our own experience and a literature search in PubMed. RESULTS: The use of RDN for treatment-resistant hypertension is based on a single randomised study with a total of 104 patients, in which the intervention group experienced a fall in blood pressure of 32/12 mm Hg, while blood pressure in the control group remained unchanged. More than 16,000 patients, particularly in Germany, have been treated on this basis. In the USA, data from a larger randomised study (n = 530) that includes sham surgery are awaited before any decision is made on whether to approve the method for use. INTERPRETATION: Before RDN can become recommended treatment in Norway, more evidence is required that the method lowers blood pressure, and that this reduces morbidity and mortality.

Novel cardiac extracellular matrix biomarkers in STEMI: Associations with ischemic injury and long-term mortality.

BACKGROUND: We aimed to determine whether serum levels of proteins related to changes in cardiac extracellular matrix (ECM) were associated with ischemic injury assessed by cardiac magnetic resonance (CMR) and mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: The concentrations of six ECM-related proteins (periostin, osteopontin, syndecan-1, syndecan-4, bone morphogenetic protein 7, and growth differentiation factor (GDF)-15) were measured in serum samples from patients on Day 1 and Month 4 after STEMI (n = 239). Ischemic injury was assessed by myocardial salvage index, microvascular obstruction, infarct size, and left ventricular function measured by CMR conducted during the initial admission (median 2 days after admission) and after 4 months. All-cause mortality was recorded after a median follow-up time of 70 months. RESULTS: Levels of periostin increased from Day 1 to Month 4 after hospitalization, while the levels of GDF-15, osteopontin, syndecan-1, and syndecan-4 declined. At both time points, high levels of syndecan-1 were associated with microvascular obstruction, large infarct size, and reduced left ventricular ejection fraction, whereas high levels of syndecan-4 at Month 4 were associated with a higher myocardial salvage index and less dilatation of the left ventricle. Higher mortality rates were associated with periostin levels at both time points, low syndecan-4 levels at Month 4, or high GDF-15 levels at Month 4. CONCLUSIONS: In patients with STEMI, we found an association between serum levels of ECM biomarkers and ischemic injury and mortality. The results provide new insight into the role ECM components play in ischemic injury following STEMI and suggests a potential for these biomarkers in prognostication after STEMI.

[Cardioprotective treatment during adjuvant cancer therapy]. / Kardioprotektiv behandling ved adjuvant kreftterapi.

BACKGROUND: Cardiac dysfunction in the form of reduced systolic and/or diastolic left ventricular function after adjuvant cancer therapy has recently attracted increasing attention. The best-known cardiotoxic agents are anthracyclines and the recombinant antibody trastuzumab. Patients treated with radiotherapy to the thorax are liable to develop coronary artery disease. There are no official guidelines for the preventive treatment of cardiac dysfunction induced by chemotherapy, antibody therapy or radiotherapy. The purpose of this article is to provide an overview of cardiac dysfunction caused by adjuvant cancer therapies and to review possible preventive therapeutic principles. MATERIAL AND METHOD: This article is based on a review of the literature derived from a search in PubMed. RESULTS: 27% of those treated with anthracyclines and trastuzumab may develop some degree of cardiac dysfunction. The figure for patients receiving radiotherapy to the thorax is more uncertain. Small-scale studies suggest that anthracycline-induced cardiac dysfunction can be prevented wholly or partially by blocking the renin-angiotensin-aldosterone system and by beta-adrenergic blockade. As yet, there are no results of prospective studies on cardiopreventive treatment during trastuzumab therapy or thoracic radiotherapy. INTERPRETATION: There is a need for randomised, placebo-controlled studies of homogeneous groups of patients in order to determine whether treatment with cardioprotective medication in parallel with chemotherapy, antibody therapy or radiotherapy can prevent or reduce cardiac dysfunction.

Rationale and design of the prevention of cardiac dysfunction during an Adjuvant Breast Cancer Therapy (PRADA) Trial.

OBJECTIVE: The PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) study is a randomized, placebo-controlled, double-blind trial to determine whether angiotensin receptor blockers (ARB), or beta-blockers or their combination may prevent the development of left ventricular (LV) dysfunction in patients on standard adjuvant treatment for early breast cancer. METHODS: Following surgical resection, 120 breast cancer patients scheduled for adjuvant epirubicin-containing chemotherapy and, if indicated, trastuzumab, will be included. They will be randomized to an ARB (candesartan), a beta-blocker (metoprolol) and matching placebos in a 2 × 2 factorial design. The primary objective of the PRADA study is to assess whether prophylactic ARB and/or beta-blockers may prevent a reduction in LV ejection fraction (EF) after adjuvant treatment of early breast cancer, as evaluated by serial cardiovascular magnetic resonance (CMR) performed at randomization, after the first chemotherapy cycle and on its completion, and for subgroups, on completion of radiotherapy or trastuzumab. Secondary outcome measures include echocardiographic indices of LV diastolic dysfunction, structural myocardial alterations assessed by CMR and changes in cardiac biomarkers. CONCLUSION: PRADA may provide new information on the prophylactic effect of ARB and beta-blockers in patients with early breast cancer regarding the risk of developing cardiac dysfunction from adjuvant cancer treatment.

Extreme altitude induces divergent mass reduction of right and left ventricle in mountain climbers.

Mountain climbing at high altitude implies exposure to low levels of oxygen, low temperature, wind, physical and psychological stress, and nutritional insufficiencies. We examined whether right ventricular (RV) and left ventricular (LV) myocardial masses were reversibly altered by exposure to extreme altitude. Magnetic resonance imaging and echocardiography of the heart, dual x-ray absorptiometry scan of body composition, and blood samples were obtained from ten mountain climbers before departure to Mount Everest or Dhaulagiri (baseline), 13.5 ± 1.5 days after peaking the mountain (post-hypoxia), and six weeks and six months after expeditions exceeding 8000 meters above sea level. RV mass was unaltered after extreme altitude, in contrast to a reduction in LV mass by 11.8 ± 3.4 g post-hypoxia (p = 0.001). The reduction in LV mass correlated with a reduction in skeletal muscle mass. After six weeks, LV myocardial mass was restored to baseline values. Extreme altitude induced a reduction in LV end-diastolic volume (20.8 ± 7.7 ml, p = 0.011) and reduced E', indicating diastolic dysfunction, which were restored after six weeks follow-up. Elevated circulating interleukin-18 after extreme altitude compared to follow-up levels, might have contributed to reduced muscle mass and diastolic dysfunction. In conclusion, the mass of the RV, possibly exposed to elevated afterload, was not changed after extreme altitude, whereas LV mass was reduced. The reduction in LV mass correlated with reduced skeletal muscle mass, indicating a common denominator, and elevated circulating interleukin-18 might be a mechanism for reduced muscle mass after extreme altitude.

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels 3 months after myocardial infarction are more strongly associated with magnetic resonance-determined ejection fraction than NTproBNP levels in the acute phase.

BACKGROUND: The relationship between levels of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and left ventricular function determined by magnetic resonance imaging (MRI) in ST-segment-elevation myocardial infarction (STEMI) is largely unknown. METHODS AND RESULTS: This was a substudy of the Norwegian Study on District Treatment of STEMI, in which patients received thrombolysis followed by early or late invasive strategy. NT-proBNP was measured at 3 days and 3 months after the myocardial infarction, and magnetic resonance imaging was performed after 3 months (n = 160). Log NT-proBNP levels at both time points were significantly associated with ejection fraction (EF) (r(2) values 0.25 and 0.42, respectively) as well as infarct size (r(2) values 0.38 and 0.47, respectively; P < .0001 for all, adjusted for confounders). Furthermore, receiver operating characteristic (ROC) curves used to analyze the ability of NT-proBNP to discriminate long-term low EF (≤40%) and large infarct size (≥15.7%), were significant at both time points (P < .001 for all). Pairwise comparison of the ROC curves showed a significantly better performance of NT-proBNP at 3 months compared with 3 days for discrimination of low EF (P = .023). CONCLUSION: Repeated measurements of NT-proBNP in STEMI patients showed that NT-proBNP levels at 3 months were more strongly associated with long-term EF and infarct size than NT-pro BNP levels after 3 days. Our data suggest that measurement of NT-proBNP 3 months after myocardial infarction is a better indicator of left ventricular function compared with NT-proBNP in the acute phase.

Assessment of left ventricular function in ST-elevation myocardial infarction by global longitudinal strain: a comparison with ejection fraction, infarct size, and wall motion score index measured by non-invasive imaging modalities.

AIMS: We aimed to compare two-dimensional global longitudinal strain (GS) with different non-invasive imaging modalities for the assessment of left ventricular function in an ST-elevation myocardial infarction population. METHODS AND RESULTS: GS was compared with ejection fraction (EF) determined by magnetic resonance imaging (MRI), standard echocardiography (echo), contrast echo, and electrocardiography-gated single-photon emission computed tomography (SPECT), as well as with MRI-determined relative infarct size and echo-determined wall motion score index (WMSI), in 163 patients participating in the NORwegian Study on District Treatment of ST-Elevation Myocardial Infarction (NORDISTEMI). The linear relation between GS and standard echo (r(2)= 0.43, P <0.001), contrast echo (r(2)= 0.38, P <0.001), and SPECT-determined EF (r(2)= 0.52, P <0.001) was almost identical as that between GS and the gold standard MRI-determined EF (r(2)= 0.47, P <0.001). GS was best associated with WMSI by echo (r(2)= 0.55, P <0.001), while the associations between GS and relative infarct size were weaker (r = 0.43, P <0.001). Receiver operator characteristics curves, used to analyse the ability of GS to discriminate low EF (≤ 40%) measured by the four different modalities, large myocardial infarction (MI ≥ 15.7%), and high WMSI (≥ 1.5), were significant for all. GS was shown to be the best predictor of low EF measured by MRI [area under the curve (AUC) 0.965], while the lowest AUC was found between GS and large MI (0.814). CONCLUSION: Global strain is associated well with EF measured by all modalities. Global strain was found to be the best predictor of low EF measured by the gold standard MRI. Since global strain is an inexpensive test, these data may be of health economic interest.

Takotsubo cardiomyopathy in acute coronary syndrome; clinical features and contribution of cardiac magnetic resonance during the acute and convalescent phase.

OBJECTIVES: Takotsubo cardiomyopathy (TTC) is a diagnostic entity that is increasingly being recognized. Data from cardiac magnetic resonance (CMR) imaging and its impact on differential diagnosis are limited. METHODS AND RESULTS: After 26 months, coronary angiography revealed normal coronary arteries and left ventriculography and/or echocardiography left ventricular dysfunction with apical ballooning in 20 patients with acute coronary syndrome (ACS). Four patients were excluded from CMR and in three patients an alternative diagnosis was revealed. Thirteen patients (all female; 60 ± 8 years) with TTC underwent a multisequential CMR, in which all showed myocardial oedema with an elevated T2 ratio in the apical region (2.4 ± 0.4; p < 0.001 vs. healthy controls), and five patients an elevated global relative enhancement (gRE; 3.7 ± 1.4; p < 0.05 vs. healthy controls). No late gadolinium enhancement (LGE) was detected on CMR. Follow-up after 132 ± 33 days showed a normalized left ventricular ejection fraction, myocardial mass, T2 ratio, and gRE in all patients. CONCLUSIONS: TTC is a small but definite group among patients with ACS and normal coronary arteries. CMR allows differentiating TTC from other causes such as myocarditis and cardiomyopathies, as well as to identify the transient increase of myocardial mass and resolution of myocardial oedema as the systolic dysfunction improves. Therefore, CMR might add valuable information for the differential diagnoses and therapeutic decision-making in patients with suspected TTC.