Fluorouracil-induced Takotsubo cardiomyopathy causing cardiogenic shock: a case report of clinical and acute cardiac magnetic resonance imaging features.

BACKGROUND: Takotsubo cardiomyopathy (TTS) is an extremely rare complication of fluorouracil containing chemotherapy regimes such as FOLFOX used for colorectal cancer, occurring in only five previous case reports. Due to its potentially fatal outcomes, yet infrequent presence in the literature, it is worthwhile reviewing the clinical features and outcomes of this phenomenon. CASE SUMMARY: A 54-year-old lady was admitted with cardiogenic shock. A cardiac magnetic resonance imaging (CMR) showed mid-ventricle to apical hypokinesis and confirmed TTS. She was managed with inotropes and non-invasive ventilation after which she recovered fully both clinically and in her CMR features 6 weeks following discharge. DISCUSSION: This is the first case showing the acute CMR features of this complication and highlights the need for awareness of this rarely occurring cardiotoxicity. It also shows the potentially fatal phenomenon can be fully reversible when diagnosed and managed promptly even in patients with metastatic cancer and critical illness.

Reappraising myocardial fibrosis in severe aortic stenosis: an invasive and non-invasive study in 133 patients.

Aims: To investigate myocardial fibrosis (MF) in a large series of severe aortic stenosis (AS) patients using invasive biopsy and non-invasive imaging. Methods and results: One hundred thirty-three patients with severe, symptomatic AS accepted for surgical aortic valve replacement underwent cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) quantification. Intra-operative left ventricular (LV) biopsies were performed by needle or scalpel, yielding tissue with (n = 53) and without endocardium (n = 80), and compared with 10 controls. Myocardial fibrosis occurred in three patterns: (i) thickened endocardium with a fibrotic layer; (ii) microscopic scars, with a subendomyocardial predominance; and (iii) diffuse interstitial fibrosis. Collagen volume fraction (CVF) was elevated (P < 0.001) compared with controls, and higher (P < 0.001) in endocardium-containing samples with a decreasing CVF gradient from the subendocardium (P = 0.001). Late gadolinium enhancement correlated with CVF (P < 0.001) but not ECV. Both LGE and ECV correlated independently (P < 0.001) with N-terminal pro-brain natriuretic peptide and high-sensitivity-troponin T. High ECV was also associated with worse LV remodelling, left ventricular ejection fraction and functional capacity. Combining high ECV and LGE better identified patients with more adverse LV remodelling, blood biomarkers and histological parameters, and worse functional capacity than each parameter alone. Conclusion: Myocardial fibrosis in severe AS is complex, but three main patterns exist: endocardial fibrosis, microscars (mainly in the subendomyocardium), and diffuse interstitial fibrosis. Neither histological CVF nor the CMR parameters ECV and LGE capture fibrosis in its totality. A combined, multi-parametric approach with ECV and LGE allows best stratification of AS patients according to the response of the myocardial collagen matrix.

Automatic quantification of the myocardial extracellular volume by cardiac computed tomography: Synthetic ECV by CCT.

BACKGROUND: The quantification of extracellular volume fraction (ECV) by Cardiac Computed Tomography (CCT) can identify changes in the myocardial interstitium due to fibrosis or infiltration. Current methodologies require laboratory blood hematocrit (Hct) measurement - which complicates the technique. The attenuation of blood (HUblood) is known to change with anemia. We hypothesized that the relationship between Hct and HUblood could be calibrated to rapidly generate a synthetic ECV without formally measuring Hct. METHODS: The association between Hct and HUblood was derived from forty non-contrast thoracic CT scans using regression analysis. Synthetic Hct was then used to calculate synthetic ECV, and in turn compared with ECV using blood Hct in a validation cohort with mild interstitial expansion due to fibrosis (aortic stenosis, n = 28, ECVCT = 28 ± 4%) and severe interstitial expansion due to amyloidosis (n = 27; ECVCT = 54 ± 11%, p < 0.001). For histological validation, synthetic ECV was correlated with collagen volume fraction (CVF) in a separate cohort with aortic stenosis (n = 18). All CT scans were performed at 120 kV and 160 mAs. RESULTS: HUblood was a good predictor of Hct (R2 = 0.47; p < 0.01), with the regression model (Hct = [0.51 * HUblood] + 17.4) describing the association. Synthetic ECV correlated well with conventional ECV (R2 = 0.96; p < 0.01) with minimal bias and 2SD difference of 5.7%. Synthetic ECV correlated as well as conventional ECV with histological CVF (both R2 = 0.50, p < 0.01). Finally, we implemented an automatic ECV plug-in for offline analysis. CONCLUSION: Synthetic ECV by CCT provides instantaneous quantification of the myocardial extracellular space without the need for blood sampling.

Circadian variation in acute myocardial infarct size assessed by cardiovascular magnetic resonance in reperfused STEMI patients.

OBJECTIVE: Clinical studies using serum cardiac biomarkers to investigate a circadian variation in acute myocardial infarct (MI) size in ST-segment elevation myocardial infarction (STEMI) patients reperfused by primary percutaneous coronary intervention (PPCI) have produced mixed results. We aimed to investigate this phenomenon using acute MI size measured by cardiovascular magnetic resonance (CMR). METHODS: Patient-level data was obtained from 4 randomized controlled trials investigating the MI-limiting effects of cardioprotective therapies in this pooled analysis. The primary analysis was performed in those patients with no pre-infarct angina; duration of ischemia >60min and <360min; Thrombolysis In Myocardial Infarction (TIMI) flow pre-PPCI ≤1; TIMI flow post-PPCI 3; and no collateral flow. RESULTS: 169 out of 376 patients with CMR data met the inclusion criteria for the primary analysis. A 24-hour circadian variation in acute MI size as a % of the area-at-risk (%AAR), after adjusting for confounders, was observed with a peak and nadir MI size in patients with symptom onset between 00:00 and 01:00 and between 12:00 and 13:00 respectively (difference from the average MI size 5.2%, 95%CI 1.1-9.4%; p=0.013). This was associated with a non-significant circadian variation in left ventricular ejection fraction (LVEF) (difference from the average LVEF 5.9%, 95%CI -0.6-2.2%, p=0.073). There was no circadian variation in MI size or LVEF in the whole cohort. CONCLUSIONS: We report a circadian variation in acute MI size assessed by CMR in a subset of STEMI patients treated by PPCI, with the largest and smallest MI size occurring in patients with symptom onset between 00:00 and 01:00 and between 12:00 and 13:00 respectively.

Residual Myocardial Iron Following Intramyocardial Hemorrhage During the Convalescent Phase of Reperfused ST-Segment-Elevation Myocardial Infarction and Adverse Left Ventricular Remodeling.

BACKGROUND: The presence of intramyocardial hemorrhage (IMH) in ST-segment-elevation myocardial infarction patients reperfused by primary percutaneous coronary intervention has been associated with residual myocardial iron at follow-up, and its impact on adverse left ventricular (LV) remodeling is incompletely understood and is investigated here. METHODS AND RESULTS: Forty-eight ST-segment-elevation myocardial infarction patients underwent cardiovascular magnetic resonance at 4±2 days post primary percutaneous coronary intervention, of whom 40 had a follow-up scan at 5±2 months. Native T1, T2, and T2* maps were acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the follow-up scan, 13/15 patients (87%) had evidence of residual iron within the infarct zone. Patients with residual iron had higher T2 in the infarct zone surrounding the residual iron when compared with those without. In patients with adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was also higher than in those without (60 [54-64] ms versus 53 [51-56] ms; P=0.025). Acute myocardial infarct size, extent of microvascular obstruction, and IMH correlated with the change in LV end-diastolic volume (Pearson's rho of 0.64, 0.59, and 0.66, respectively; P=0.18 and 0.62, respectively, for correlation coefficient comparison) and performed equally well on receiver operating characteristic curve for predicting adverse LV remodeling (area under the curve: 0.99, 0.94, and 0.95, respectively; P=0.19 for receiver operating characteristic curve comparison). CONCLUSIONS: The majority of ST-segment-elevation myocardial infarction patients with IMH had residual myocardial iron at follow-up. This was associated with persistently elevated T2 values in the surrounding infarct tissue and adverse LV remodeling. IMH and residual myocardial iron may be potential therapeutic targets for preventing adverse LV remodeling in reperfused ST-segment-elevation myocardial infarction patients.

Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement.

BACKGROUND: Calcific aortic stenosis (cAS) affects 3% of individuals aged >75 years, leading to heart failure and death unless the valve is replaced. Wild-type transthyretin cardiac amyloid is also a disorder of ageing individuals. Prevalence and clinical significance of dual pathology are unknown. This study explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance. METHODS AND RESULTS: A total of 146 patients with severe AS requiring surgical valve replacement underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had cAS (75±6 years; 57% men). Amyloid was sought histologically using Congo red staining and then typed using immunohistochemistry and mass spectrometry; patients with amyloid underwent clinical evaluation including genotyping and (99m)TC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy. Amyloid was identified in 6 of 146 patients, all with cAS and >65 years (prevalence 5.6% in cAS >65). All 6 patients had wild-type transthyretin amyloid (mean age 75 years; range, 69-85; 4 men), not suspected on echocardiography. Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans demonstrated cardiac localization in all 4 patients who had this investigation (2 died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus 7.5% in cAS; 6.9% in age >65 years). In univariable analyses, the presence of transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5 [95% confidence interval, 2.5-35.8]; P=0.001). CONCLUSIONS: Occult wild-type transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged >65 years undergoing surgical aortic valve replacement and was associated with a poor outcome.

Automated Extracellular Volume Fraction Mapping Provides Insights Into the Pathophysiology of Left Ventricular Remodeling Post-Reperfused ST-Elevation Myocardial Infarction.

BACKGROUND: Whether the remote myocardium of reperfused ST-segment elevation myocardial infarction (STEMI) patients plays a part in adverse left ventricular (LV) remodeling remains unclear. We aimed to use automated extracellular volume fraction (ECV) mapping to investigate whether changes in the ECV of the remote (ECVR emote) and infarcted myocardium (ECVI nfarct) impacted LV remodeling. METHODS AND RESULTS: Forty-eight of 50 prospectively recruited reperfused STEMI patients completed a cardiovascular magnetic resonance at 4±2 days and 40 had a follow-up scan at 5±2 months. Twenty healthy volunteers served as controls. Mean segmental values for native T1, T2, and ECV were obtained. Adverse LV remodeling was defined as ≥20% increase in LV end-diastolic volume. ECVR emote was higher on the acute scan when compared to control (27.9±2.1% vs 26.4±2.1%; P=0.01). Eight patients developed adverse LV remodeling and had higher ECVR emote acutely (29.5±1.4% vs 27.4±2.0%; P=0.01) and remained higher at follow-up (28.6±1.5% vs 26.6±2.1%; P=0.02) compared to those without. Patients with a higher ECVR emote and a lower myocardial salvage index (MSI) acutely were significantly associated with adverse LV remodeling, independent of T1Remote, T1Core and microvascular obstruction, whereas a higher ECVI nfarct was significantly associated with worse wall motion recovery. CONCLUSIONS: ECVR emote was increased acutely in reperfused STEMI patients. Those with adverse LV remodeling had higher ECVR emote acutely, and this remained higher at follow-up than those without adverse LV remodeling. A higher ECVR emote and a lower MSI acutely were significantly associated with adverse LV remodeling whereas segments with higher ECVI nfarct were less likely to recover wall motion.

Quantifying the Area at Risk in Reperfused ST-Segment-Elevation Myocardial Infarction Patients Using Hybrid Cardiac Positron Emission Tomography-Magnetic Resonance Imaging.

BACKGROUND: Hybrid positron emission tomography and magnetic resonance allows the advantages of magnetic resonance in tissue characterizing the myocardium to be combined with the unique metabolic insights of positron emission tomography. We hypothesized that the area of reduced myocardial glucose uptake would closely match the area at risk delineated by T2 mapping in ST-segment-elevation myocardial infarction patients. METHODS AND RESULTS: Hybrid positron emission tomography and magnetic resonance using (18)F-fluorodeoxyglucose (FDG) for glucose uptake was performed in 21 ST-segment-elevation myocardial infarction patients at a median of 5 days. Follow-up scans were performed in a subset of patients 12 months later. The area of reduced FDG uptake was significantly larger than the infarct size quantified by late gadolinium enhancement (37.2±11.6% versus 22.3±11.7%; P<0.001) and closely matched the area at risk by T2 mapping (37.2±11.6% versus 36.3±12.2%; P=0.10, R=0.98, bias 0.9±4.4%). On the follow-up scans, the area of reduced FDG uptake was significantly smaller in size when compared with the acute scans (19.5 [6.3%-31.8%] versus 44.0 [21.3%-55.3%]; P=0.002) and closely correlated with the areas of late gadolinium enhancement (R 0.98) with a small bias of 2.0±5.6%. An FDG uptake of ≥45% on the acute scans could predict viable myocardium on the follow-up scan. Both transmural extent of late gadolinium enhancement and FDG uptake on the acute scan performed equally well to predict segmental wall motion recovery. CONCLUSIONS: Hybrid positron emission tomography and magnetic resonance in the reperfused ST-segment-elevation myocardial infarction patients showed reduced myocardial glucose uptake within the area at risk and closely matched the area at risk delineated by T2 mapping. FDG uptake, as well as transmural extent of late gadolinium enhancement, acutely can identify viable myocardial segments.

Automatic Measurement of the Myocardial Interstitium: Synthetic Extracellular Volume Quantification Without Hematocrit Sampling.

OBJECTIVES: The authors sought to generate a synthetic extracellular volume fraction (ECV) from the relationship between hematocrit and longitudinal relaxation rate of blood. BACKGROUND: ECV quantification by cardiac magnetic resonance (CMR) measures diagnostically and prognostically relevant changes in the extracellular space. Current methodologies require blood hematocrit (Hct) measurement-a complication to easy clinical application. We hypothesized that the relationship between Hct and longitudinal relaxation rate of blood (R1 = 1/T1blood) could be calibrated and used to generate a synthetic ECV without Hct that was valid, user-friendly, and prognostic. METHODS: Proof-of-concept: 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts. Histology cohort: 18 patients with severe aortic stenosis with histology obtained during valve replacement. Outcome cohort: For comparison with external outcome data, we applied synthetic ECV to 1,172 consecutive patients (median follow-up 1.7 years; 74 deaths). All underwent CMR scanning at 1.5-T with ECV calculation from pre- and post-contrast T1 (blood and myocardium) and venous Hct. RESULTS: Proof-of-concept: In the derivation cohort, native R1blood and Hct showed a linear relationship (R(2) = 0.51; p < 0.001), which was used to create synthetic Hct and ECV. Synthetic ECV correlated well with conventional ECV (R(2) = 0.97; p < 0.001) without bias. These results were maintained in the validation cohort. Histology cohort: Synthetic and conventional ECV both correlated well with collagen volume fraction measured from histology (R(2) = 0.61 and 0.69, both p < 0.001) with no statistical difference (p = 0.70). Outcome cohort: Synthetic ECV related to all-cause mortality (hazard ratio 1.90; 95% confidence interval 1.55 to 2.31; for every 5% increase in ECV). Finally, we engineered a synthetic ECV tool, generating automatic ECV maps during image acquisition. CONCLUSIONS: Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.

T1 mapping and T2 mapping at 3T for quantifying the area-at-risk in reperfused STEMI patients.

BACKGROUND: Whether T1-mapping cardiovascular magnetic resonance (CMR) can accurately quantify the area-at-risk (AAR) as delineated by T2 mapping and assess myocardial salvage at 3T in reperfused ST-segment elevation myocardial infarction (STEMI) patients is not known and was investigated in this study. METHODS: 18 STEMI patients underwent CMR at 3T (Siemens Bio-graph mMR) at a median of 5 (4-6) days post primary percutaneous coronary intervention using native T1 (MOLLI) and T2 mapping (WIP #699; Siemens Healthcare, UK). Matching short-axis T1 and T2 maps covering the entire left ventricle (LV) were assessed by two independent observers using manual, Otsu and 2 standard deviation thresholds. Inter- and intra-observer variability, correlation and agreement between the T1 and T2 mapping techniques on a per-slice and per patient basis were assessed. RESULTS: A total of 125 matching T1 and T2 mapping short-axis slices were available for analysis from 18 patients. The acquisition times were identical for the T1 maps and T2 maps. 18 slices were excluded due to suboptimal image quality. Both mapping sequences were equally prone to susceptibility artifacts in the lateral wall and were equally likely to be affected by microvascular obstruction requiring manual correction. The Otsu thresholding technique performed best in terms of inter- and intra-observer variability for both T1 and T2 mapping CMR. The mean myocardial infarct size was 18.8 ± 9.4 % of the LV. There was no difference in either the mean AAR (32.3 ± 11.5 % of the LV versus 31.6 ± 11.2 % of the LV, P = 0.25) or myocardial salvage index (0.40 ± 0.26 versus 0.39 ± 0.27, P = 0.20) between the T1 and T2 mapping techniques. On a per-slice analysis, there was an excellent correlation between T1 mapping and T2 mapping in the quantification of the AAR with an R(2) of 0.95 (P < 0.001), with no bias (mean ± 2SD: bias 0.0 ± 9.6 %). On a per-patient analysis, the correlation and agreement remained excellent with no bias (R(2) 0.95, P < 0.0001, bias 0.7 ± 5.1 %). CONCLUSIONS: T1 mapping CMR at 3T performed as well as T2 mapping in quantifying the AAR and assessing myocardial salvage in reperfused STEMI patients, thereby providing an alternative CMR measure of the the AAR.

Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

BACKGROUND: Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension. METHODS: In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers. RESULTS: Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m(2); female > 78 g/m(2)). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001). CONCLUSION: In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.

Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis.

BACKGROUND: Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed. OBJECTIVES: To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT. METHODS: Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area). RESULTS: ECVCT and ECVCMR results were well correlated (r(2) = 0.85 vs r(2) = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001). CONCLUSION: Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis.

Mineralocorticoid receptor antagonist pretreatment to MINIMISE reperfusion injury after ST-elevation myocardial infarction (the MINIMISE STEMI Trial): rationale and study design.

Novel therapies capable of reducing myocardial infarct (MI) size when administered prior to reperfusion are required to prevent the onset of heart failure in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). Experimental animal studies have demonstrated that mineralocorticoid receptor antagonist (MRA) therapy administered prior to reperfusion can reduce MI size, and MRA therapy prevents adverse left ventricular (LV) remodeling in post-MI patients with LV impairment. With these 2 benefits in mind, we hypothesize that initiating MRA therapy prior to PPCI, followed by 3 months of oral MRA therapy, will reduce MI size and prevent adverse LV remodeling in STEMI patients. The MINIMISE-STEMI trial is a prospective, randomized, double-blind, placebo-controlled trial that will recruit 150 STEMI patients from four centers in the United Kingdom. Patients will be randomized to receive either an intravenous bolus of MRA therapy (potassium canrenoate 200 mg) or matching placebo prior to PPCI, followed by oral spironolactone 50 mg once daily or matching placebo for 3 months. A cardiac magnetic resonance imaging scan will be performed within 1 week of PPCI and repeated at 3 months to assess MI size and LV remodeling. Enzymatic MI size will be estimated by the 48-hour area-under-the-curve serum cardiac enzymes. The primary endpoint of the study will be MI size on the 3-month cardiac magnetic resonance imaging scan. The MINIMISE STEMI trial will investigate whether early MRA therapy, initiated prior to reperfusion, can reduce MI size and prevent adverse post-MI LV remodeling.

Noncontrast myocardial T1 mapping using cardiovascular magnetic resonance for iron overload.

PURPOSE: To explore the use and reproducibility of magnetic resonance-derived myocardial T1 mapping in patients with iron overload. MATERIALS AND METHODS: The research received ethics committee approval and all patients provided written informed consent. This was a prospective study of 88 patients and 67 healthy volunteers. Thirty-five patients underwent repeat scanning for reproducibility. T1 mapping used the shortened modified Look-Locker inversion recovery sequence (ShMOLLI) with a second, confirmatory MOLLI sequence in the reproducibility group. T2 * was performed using a commercially available sequence. The analysis of the T2 * interstudy reproducibility data was performed by two different research groups using two different methods. RESULTS: Myocardial T1 was lower in patients than healthy volunteers (836 ± 138 msec vs. 968 ± 32 msec, P < 0.0001). Myocardial T1 correlated with T2 * (R = 0.79, P < 0.0001). No patient with low T2 * had normal T1 , but 32% (n = 28) of cases characterized by a normal T2 * had low myocardial T1 . Interstudy reproducibility of either T1 sequence was significantly better than T2 *, with the results suggesting that the use of T1 in clinical trials could decrease potential sample sizes by 7-fold. CONCLUSION: Myocardial T1 mapping is an alternative method for cardiac iron quantification. T1 mapping shows the potential for improved detection of mild iron loading. The superior reproducibility of T1 has potential implications for clinical trial design and therapeutic monitoring.

Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: This study aimed to determine whether remote ischemic conditioning (RIC) initiated prior to primary percutaneous coronary intervention (PPCI) could reduce myocardial infarct (MI) size in patients presenting with ST-segment elevation myocardial infarction. BACKGROUND: RIC, using transient limb ischemia and reperfusion, can protect the heart against acute ischemia-reperfusion injury. Whether RIC can reduce MI size, assessed by cardiac magnetic resonance (CMR), is unknown. METHODS: We randomly assigned 197 ST-segment elevation myocardial infarction patients with TIMI (Thrombolysis In Myocardial Infarction) flow grade 0 to receive RIC (four 5-min cycles of upper arm cuff inflation/deflation) or control (uninflated cuff placed on upper arm for 40 min) protocols prior to PPCI. The primary study endpoint was MI size, measured by CMR in 83 subjects on days 3 to 6 after admission. RESULTS: RIC reduced MI size by 27%, when compared with the MI size of control subjects (18.0 ± 10% [n = 40] vs. 24.5 ± 12.0% [n = 43]; p = 0.009). At 24 h, high-sensitivity troponin T was lower with RIC (2,296 ± 263 ng/l [n = 89] vs. 2,736 ± 325 ng/l [n = 84]; p = 0.037). RIC also reduced the extent of myocardial edema measured by T2-mapping CMR (28.5 ± 9.0% vs. 35.1 ± 10.0%; p = 0.003) and lowered mean T2 values (68.7 ± 5.8 ms vs. 73.1 ± 6.1 ms; p = 0.001), precluding the use of CMR edema imaging to correctly estimate the area at risk. Using CMR-independent coronary angiography jeopardy scores to estimate the area at risk, RIC, when compared with the control protocol, was found to significantly improve the myocardial salvage index (0.42 ± 0.29 vs. 0.28 ± 0.29; p = 0.03). CONCLUSIONS: This randomized study demonstrated that in ST-segment elevation myocardial infarction patients treated by PPCI, RIC, initiated prior to PPCI, reduced MI size, increased myocardial salvage, and reduced myocardial edema.

Reproducibility of native myocardial T1 mapping in the assessment of Fabry disease and its role in early detection of cardiac involvement by cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) derived native myocardial T1 is decreased in patients with Fabry disease even before left ventricular hypertrophy (LVH) occurs and may be the first non-invasive measure of myocyte sphingolipid storage. The relationship of native T1 lowering prior to hypertrophy and other candidate early phenotype markers are unknown. Furthermore, the reproducibility of T1 mapping has never been assessed in Fabry disease. METHODS: Sixty-three patients, 34 (54%) female, mean age 48±15 years with confirmed (genotyped) Fabry disease underwent CMR, ECG and echocardiographic assessment. LVH was absent in 25 (40%) patients. Native T1 mapping was performed with both Modified Look-Locker Inversion recovery (MOLLI) sequences and a shortened version (ShMOLLI) at 1.5 Tesla. Twenty-one patients underwent a second scan within 24 hours to assess inter-study reproducibility. Results were compared with 63 healthy age and gender-matched volunteers. RESULTS: Mean native T1 in Fabry disease (LVH positive), (LVH negative) and healthy volunteers was 853±50 ms, 904±46 ms and 968±32 ms (for all p<0.0001) by ShMOLLI sequences. Native T1 showed high inter-study, intra-observer and inter-observer agreement with intra-class correlation coefficients (ICC) of 0.99, 0.98, 0.97 (ShMOLLI) and 0.98, 0.98, 0.98 (MOLLI). In Fabry disease LVH negative individuals, low native T1 was associated with reduced echocardiographic-based global longitudinal speckle tracking strain (-18±2% vs -22±2%, p=0.001) and early diastolic function impairment (E/E'=7 [6-8] vs 5 [5-6], p=0.028). CONCLUSION: Native T1 mapping in Fabry disease is a reproducible technique. T1 reduction prior to the onset of LVH is associated with early diastolic and systolic changes measured by echocardiography.

T1 Mapping for Characterization of Intracellular and Extracellular Myocardial Diseases in Heart Failure.

Heart failure (HF) is a major and growing cause of morbidity and mortality. Despite initial successes, there have been few recent therapeutic advances. A better understanding of HF pathophysiology is needed with renewed focus on the myocardium itself. A new imaging technique is now available that holds promise. T1 mapping is a cardiovascular magnetic resonance (CMR) technique for non-invasive myocardial tissue characterization. T1 alters with disease. Pre-contrast (native) T1 changes with a number of processes such as fibrosis, edema and infiltrations. If a post contrast scan is also done, the extracellular volume fraction (ECV) can be measured, a direct measure of the interstitium and its reciprocal, the cell volume. This dichotomy is fundamental - and now measurable promising more targeted therapy and new insights into disease biology.

Long-term survival in patients undergoing percutaneous interventions with or without intracoronary pressure wire guidance or intracoronary ultrasonographic imaging: a large cohort study.

IMPORTANCE: Intracoronary pressure wire-derived measurements of fractional flow reserve (FFR) and intravascular ultrasonography (IVUS) provide functional and anatomical information that can be used to guide coronary stent implantation. Although these devices are widely used and recommended by guidelines, limited data exist about their effect on clinical end points. OBJECTIVE: To determine the effect on long-term survival of using FFR and IVUS during percutaneous coronary intervention (PCI). DESIGN AND SETTING: Cohort study based on the pan-London (United Kingdom) PCI registry. In total, 64,232 patients are included in this registry covering the London, England, area. PARTICIPANTS: All patients (n = 41,688) who underwent elective or urgent PCI in National Health Service hospitals in London between January 1, 2004, and July 31, 2011, were included. Patients with ST-segment elevation myocardial infarction (n = 11,370) were excluded. INTERVENTIONS: Patients underwent PCI guided by angiography (visual lesion assessment) alone, PCI guided by FFR, or IVUS-guided PCI. MAIN OUTCOMES AND MEASURES: The primary end point was all-cause mortality at a median of 3.3 years. RESULTS: Fractional flow reserve was used in 2767 patients (6.6%) and IVUS was used in 1831 patients (4.4%). No difference in mortality was observed between patients who underwent angiography-guided PCI compared with patients who underwent FFR-guided PCI (hazard ratio, 0.88; 95% CI, 0.67-1.16; P = .37). Patients who underwent IVUS had a slightly higher adjusted mortality (hazard ratio, 1.39; 95% CI, 1.09-1.78; P = .009) compared with patients who underwent angiography-guided PCI. However, this difference was no longer statistically significant in a propensity score-based analysis (hazard ratio, 1.33; 95% CI, 0.85-2.09; P = .25). The mean (SD) number of implanted stents was lower in the FFR group (1.1 [1.2] stents) compared with the IVUS group (1.6 [1.3]) and the angiography-guided group (1.7 [1.1]) (P < .001). CONCLUSIONS AND RELEVANCE: In this large observational study, FFR-guided PCI and IVUS-guided PCI were not associated with improved long-term survival compared with standard angiography-guided PCI. The use of FFR was associated with the implantation of fewer stents.