Hypertrophic cardiomyopathy (HCM) with midventricular hypertrophy is an uncommon phenotypic variant of the disease. Midventricular hypertrophy predisposes to intracavitary obstruction and downstream hemodynamic sequelae.We present a case of HCM with midventricular hypertrophy and obstruction diagnosed after a CT scan of the abdomen incidentally revealed a filling defect in the left ventricular apex. Transthoracic echocardiography demonstrated mid left ventricular hypertrophy and obstruction, as well as an aneurysmal apex containing a large thrombus. Cardiovascular MRI showed a spade-shaped left ventricle with midcavitary obliteration, an infarcted apex and regions of myocardial fibrosis. Due to the risk of embolization and a relative contraindication to anticoagulation, the patient underwent surgery including thrombectomy, septal myectomy and aneurysmal ligation.Hypertrophic cardiomyopathy with midventricular hypertrophy leads to cavity obstruction, increased apical wall tension, ischemia and ultimately fibrosis. Over time, patchy apical fibrosis can develop into a confluent scar resembling a transmural myocardial infarction in the left anterior descending coronary artery distribution. Aneurysmal remodeling of the left ventricular apex potentiates thrombus formation and risk of cardioembolism. For these reasons, hypertrophic cardiomyopathy with midventricular obstruction portends a particularly poor prognosis and should be recognized early in the disease process. Hypertrophic cardiomyopathy is defined as a myocardial disease characterized by unexplained left ventricular hypertrophy in association with non-dilated ventricular chambers . The dis2) status-post gastric bypass surgery over ten years prior to presentation was admitted for evaluation of an upper gastrointestinal bleed. Postoperatively following gastric bypass surgery, the patient became hemodynamically unstable and developed acute kidney injury. Although her renal function improved, the underlying etiology of her postoperative complications remained unknown. An abnormal electrocardiogram noted several years later suggested a prior myocardial infarction, retrospectively hypothesized incurred perioperatively. The abnormal electrocardiogram prompted invasive coronary angiography which showed no evidence of obstructive coronary artery disease. During the current admission for upper gastrointestinal bleeding, an abdominal CT scan with intravenous contrast serendipitously revealed a filling defect in the left ventricular apex. Transthoracic echocardiography confirmed the presence of a large, heterogeneous apical mass and additionally showed midventricular hypertrophy measuring 20 mm in the interventricular septum, resulting in systolic apposition of the midventricular segments  with midcavity hypertrophy , a measured ejection fraction of 65% and an aneurysmal apex , oxygen supply-demand mismatch, ischemia and ultimately infarction and fibrosis. Patients with HCM also have abnormally thickened intramural arteries with decreased luminal size . CoupledThe increasingly utilized CMR technique of native T1 mapping characterizes myocardium based on quantitative T1 relaxation times, altered by the presence of fibrosis, without the need for intravenous gadolinium contrast agent. Increased T1 relaxation times in hypertrophic cardiomyopathy correlate with abnormalities in left ventricular systolic function even in the absence of late gadolinium enhancement . In the Patients with HCM and midventricular obstruction may exhibit a characteristic echocardiographic Doppler pattern of blood flow in the left ventricle . Due to This morphological variant of HCM deserves clinical recognition. In a Japanese study  of 490 cMaron et al.  have queHypertrophic cardiomyopathy with midventricular hypertrophy and obstruction is a relatively uncommon variant of HCM that may lead to an infarcted apex and aneurysm formation. Mid ventricular obstruction with apical aneurysm formation predisposes to thrombus formation and portends a poor prognosis. Repercussions of aneurysm formation included ventricular arrhythmias, thromboembolism, predisposition to end stage disease and death. Physicians should be aware of this variant and consider these patients to be at higher risk when making management decisions.


Background: Intravenous recombinant tissue plasminogen activator (rt-PA) is an approved treatment for acute ischemic stroke within 4.5 h of symptoms onset. Decompressive craniectomy (DC) has been shown as an effective therapeutic modality in malignant middle cerebral artery (MCA) infarction. As rt-PA could result in hemorrhagic complication during or after any surgery DC may be associated with severe bleeding after intravenous thrombolysis.Case Description: A 57-year-old woman was presented 90 min after the sudden onset of left hemiplegia. Despite intravenous thrombolytic therapy, she lost consciousness within 48 h and brain CT scan showed a right malignant MCA infarction associated with a small bleeding. DC was performed without any complication. The patient improved dramatically.Conclusion: DC could be done safety for malignant MCA infarction after unsuccessful intravenous thrombolytic therapy even the later was complicated with intra-infarction hemorrhage. Herein, we present a case of DC after unsuccessful intravenous recombinant tissue plasminogen activator (rt-PA) treatment of MCA infarction.Intravenous thrombolysis is approved for acute ischemic stroke within 4.5 h of onset in our hospital. Decompressive craniectomy (DC) was shown to be lifesaving and effective for malignant middle cerebral artery (MCA) infarction.th day of operation she was discharged with NIHSS 11. Three months later, she was admitted for cranioplasty. She was alert with NIHSS 4. The cranioplasty was performed without any complication.The case we present here is about a 57-year-old woman who was presented with sudden onset of right hemiplegia. On physical examination, she was alert with right hemiplegia, right facial paresis, and severe aphasia . She had untreated mitral valve stenosis. The time between the onset of symptoms and admission was 90 min. Emergent brain CT scan showed effacement of left MCA territory . Thrombo1-4Recently, pooled data from three European randomized controlled trials  have shown that not only DC has dramatically decreased the mortality rate of malignant MCA infarction from 80% to 20%, but also improved patients’ functional outcome.5,6 Despite short half-life of rt-PA (5 min), its fibrinolytic effect may persist up to 24–48 h.7 Symptomatic intra-cerebral hemorrhage is the most severe complication of thrombolytic therapy with rt-PA that complicates 6.4% of patients within 36 h of treatment.8 Therefore, there is a major concern about DC after thrombolysis because it may be complicated by severe hemorrhage during or after surgery or result in progression of the preexisting intracranial hematoma. Williams et al. represented two cases of malignant MCA infarction, managed by DC after 24 h of intravenous rt-PA administration. The procedures were reported without complication, and both patients improved.9 Fisher et al. showed that the mortality and major complications after DC in malignant MCA infarction were not different between patients with prior intra-arterial thrombolysis (IAT) and those without prior IAT.10 One of their patients with prior IAT was complicated with severe hemorrhage during DC probably due to pretreatment with dual anticoagulant therapy of aspirin and plavix rather than to IAT alone.10 Takeuchi et al. also revealed that patients with malignant MCA infarction there was no difference for new intracranial bleeding and worsening of pre-existing intra-cerebral hemorrhage between the DC patients with prior intravenous thrombolysis (IVT) and those without prior IVT.11 In both studies, DC resulted in a favorable outcome in patients with prior IVT or IAT similar to HAMLET study.10,11 Our patient also profited DC without any hemorrhagic complication despite prior IVT. These results may suggest the safety and efficacy of DC after IVT or IAT for malignant MCA infarction.Recombinant t-PA enhances local fibrinolysis by converting plasminogen to plasmin. Its half-life is <5 min. Its clearance rate is 380–570 mL/min and is dominantly through the liver.7 previous studies have shown that DC even within first 48 h of rt-PA administration could be performed safely.9-11 Fibrinogen degradation products (FDP), α2-plasmin inhibitor, and the plasmin-α2-plasmin inhibitor change dramatically during 24 h and they retain to their baseline level within 24 h.7 It is recommended to perform DC within 48 h of malignant MCA infarction occurrence.4,12 It is assumed that the optimal time for DC could be between 24 and 48 h after rt-PA administration. In addition, the serum levels of FDP, α2-plasmin inhibitor, and the plasmin-α2-plasmin inhibitor before DC could be helpful for precise decision of optimal time of DC.The optimal time of DC after thrombolysis remains to define. Although the fibrinolytic effect of rt-PA could persist up to 24-48 h,


Here, we apply a non-invasive approach to determining VVCR in pediatric subjects with PH.Pediatric pulmonary hypertension (PH) remains a disease with high morbidity and mortality in children. Understanding ventricular-vascular coupling, a measure of how well matched the ventricular and vascular function are, may elucidate pathway leading to right heart failure. Ventricular vascular coupling ratio (VVCR), comprised of effective elastance (Em) and compared to VVCR estimated by catheterization-derived single beat estimation (VVCRs). Indexed pulmonary vascular resistance (PVRi) and pulmonary vascular reactivity were determined during the catheterization procedure. Pearson correlation coefficients were calculated between PVRi and VVCRm. Receiver operating characteristic (ROC) curve analysis determined the diagnostic value of VVCRm in predicting vascular reactivity.This retrospective study included PH subjects who had a cardiovascular magnetic resonance (CMR) study within 14 days of cardiac catheterization. PH was defined as mean pulmonary artery pressure (mPAP) ≥ 25 mmHg on prior or current catheterization. A non-invasive measure of VVCR was derived from CMR-only (VVCRm (range 0.43–2.82) increased with increasing severity as defined by PVRi (p < 0.001), and was highly correlated with PVRi . Regression of VVCRm and PVRi demonstrated differing lines when separated by reactivity. VVCRm was significantly correlated with VVCRs . ROC curve analysis showed high accuracy of VVCRm in determining vascular reactivity (VVCR = 0.85 had a sensitivity of 100 % and a specificity of 80 %) with an area under the curve of 0.89 (p = 0.008).Seventeen subjects  were identified between January 2009-August 2013 for inclusion with equal gender distributions. Mean mPAP was 35 mmHg ± 15 and PVRi was 8.5 Woods unit x m2 ± 7.8. VVCRm in pediatrics is feasible. Pulmonary vascular non-reactivity may be contribute to ventricular-vascular decoupling in severe PH. Therapeutic intervention to maintain a low vascular afterload in reactive patients may preserve right ventricular functional reserve and delay the onset of RV-PA decoupling. Use of VVCRm may have significant prognostic implication.Measurement of VVCR Pulmonary hypertension (PH) in children remains an incurable disease with poor long-term prognosis that crosses all racial and socioeconomic backgrounds . PH affeThe ventricular-vascular coupling ratio (VVCR), the ratio of contractility to afterload, reflects the ventricular functional reserve in response to a rising afterload in order to maintain cardiac output. VVCR has been recently shown to be prognostic of impending RV failure . ConventIn this study, we apply Sanz’s approach to the pediatric population with PH to determine VVCR in the right heart and compare it to the modified single beat method. Determining the VVCR by noninvasive measures is critical in the pediatric population. The lack of exposure to radiation, anesthesia, and intracardiac catheter manipulations with CMR are important concerns to consider, as these patients often undergo multiple catheterization procedures throughout their lives to establish diagnosis and monitor responses to medications. As a result, the aims of this study are to: 1) determine if the noninvasive CMR approach to VVCR determination is feasible in a pediatric population, 2) understand how the technique compares with the more established single beat estimation method, and 3) determine the ability of the CMR-based VVCR method to predict patient outcome, as measured by acute vasoreactivity.The medical records of children cared for in the Pulmonary Hypertension Program at Children’s Hospital Colorado were retrospectively reviewed from January 2009 to August 2013 for any patient, age 0 days to 65 years, who underwent a right heart catheterization (RHC) for pulmonary hypertension. The diagnosis of PH is defined by a previous or present cardiac catheterization showing mean pulmonary artery pressure (mPAP) ≥ 25 mmHg. Two hundred and forty-two patients were identified. Of these, we identified seventeen subjects who had a CMR study performed within 14 days of a cardiac catheterization. Exclusion criteria were: 1) pulmonary valve or pulmonary arterial stenosis; 2) previous surgical or catheterization intervention on the pulmonary valve or pulmonary artery; 3) pulmonary artery stenosis 4) previous right ventriculotomy; 5) congenital heart disease more complex than simple atrial septal defect; 6) more than mild pulmonary insufficiency; 7) severe left-sided obstruction that can potentially cause elevated pulmonary pressures; 8) chronic thrombolic pulmonary hypertension and 9) presence of arrhythmias. We excluded anatomic stenosis of the pulmonary circulation and chronic thrombolic PH because this is a study of vascular remodeling in the presence of high resistance rather than a study of the effects of anatomic constrictions or obstruction to flow. This study was carried out with the approval of the Colorado Institutional Review Board.a, representing afterload encountered by the ventricle and is a combination of resistance, compliance, and the time interval between systole and diastole) and the right maximal end-systolic elastance  [VVCR is composed of the arterial elastance (Ectility) . In adulctility) . ElevateCMR studies were performed either on a 1.5 Tesla Siemens Avanto  or a 1.5 Tesla Philips Achieva  scanner. Five of the youngest subjects were sedated for the CMR. Standard horizontal long axis and short axis images were obtained at end-expiration with a parallel stack of serial images acquired from the base to the apex . DependiRm=ESVSV . RV ejecDecrease in mPAP of ≥ 20 %,Unchanged or increased cardiac index, andDecreased or unchanged PVR to systemic vascular resistance ratio.All subjects were under general anesthesia for the RHC. A balloon-wedge catheter was introduced through the femoral vein or internal jugular vein and advanced into the right heart employing standard methodologies. Hemodynamic measurements were obtained, including right ventricular end-diastolic pressure, mPAP, transpulmonary gradient, and PCWP pressures. The Fick equation, with cardiac index calculated as cardiac output divided by body surface area, was used to determine cardiac output. PVR was calculated as the difference between mPAP and PCWP, all divided by the cardiac index. Indexed PVR is the product of PVR and body surface area. Part of the standard PH right heart catheterization at our institution is the determination of vascular reactivity with data obtained at room air and under vasodilator challenge. The vasodilator challenge involves 80–100 % oxygen or oxygen + inhaled nitric oxide . Vascular reactivity was determined by the Barst criteria , defineds. The single beat method was first proposed by Takeuchi et al. [es using the pressure tracing for a single beat. In this method, the theoretical maximum pressure the ventricle can generate is found by fitting a sinusoid to the iso-volumetric regions of the pressure tracing. The maximum of the sinusoid (Pmax) is used with the end-systolic ventricular pressure (Pes) to compute the slope of the end-systolic pressure volume relationship, Ees.  to yield VVCRi et al.  in whiches. Fig. . This meWe modified this technique even further. Closely examining Fig. Further given the definition , 192\docs asThus, we can take the ratio of equations  and 2)  2) to obs as a simple ratio of the inverse of maximum isovolumic pressure to end-systolic pressure.Thus, equation  approximm and PVRi. In addition, Pearson correlation coefficients were calculated to determine strength of the relationship. Receiver-operating characteristic (ROC) curve analysis was used to determine the cut-off value of VVCRm that was most frequently associated with pulmonary vascular reactivity, determined by the Barst criteria. This cut-off value maximizes the sum of sensitivity and specificity, which is equivalent to maximizing the difference between the sensitivity of the prognostic factor and the sensitivity that the prognostic factor would have if it did no better than random chance. Statistical significance was set at a p-value of 0.05 or less.Statistical analysis was performed using the Statistical Analysis System . Data were evaluated for normality using a Shapiro-Wilk test. Normally distributed, continuous data are presented as mean with standard deviation and categorical variables are presented as frequencies and percentages. Regression analysis was performed to estimate the relationship between VVCRSeventeen subjects were identified for inclusion with equal gender distributions Table . Age ranm ranged from 0.84 to 3.29. While regression of VVCRm and PVRi showed a linear relationship, a difference was seen in the slopes of the relationship between those who were reactive and those who were non-reactive  .VVCR01) Fig. . Heart rm in determining vascular reactivity. VVCRm of 0.85 had a sensitivity of 100 % and a specificity of 80 %. The area under the curve is 0.89 (p = 0.008), suggesting good discrimination between those who were and were not reactive.Receiver operating characteristic curve analysis Figs.  and 4 rem. In addition, the median WHO-FC was 2 for the reactive subjects, and 3 for the non-reactive subjects. PVRi was not statistically significantly different, although the mean PVRi among the non-reactive subjects was more than double that of the reactive subjects. Similarly, although the length of disease was not statistically different between the two groups, the mean duration among the non-reactive subjects was almost twice that of the reactive subjects.Table In this paper, we have shown that the measurement of VVCR by CMR data in children is feasible. Furthermore, our study shows that VVCR derived from CMR data correlates with VVCR derived from the single beat estimation from catheterization-derived pressure tracings. The most intriguing finding here is the potential of noninvasively derived VVCR in predicting vasoreactivity. Acute vasoreactivity have been shown to independently predict transplant-free survival .es > Ea. In this state, the maximum stroke work is accomplished by minimum oxygen consumption [a > Ees and stroke volume begins to fall. The concept of ventricular vascular coupling is essential to understanding PH, since this disease exemplifies the breakdown of the complex interaction between the vasculature and ventricle, ultimately resulting in RV failure. However, in clinical medicine, PVR continues to be primary parameter in which PH state is accessed. This is due to the labor-intensive, invasive nature of determining VVCR by establishing pressure-volume loops. Sanz proposed a non-invasive approach to determine VVCR based on CMR data [es when using the Sanz’ approach [m and PVR. In contrast, our data shows a linear relationship. This may simply due to our small patient population. Both Sanz’s and our data covers a large range of PVRi, but with a significant sample difference of 150 in Sanz’s study compared to our 17 subjects.In the normal RV-PA axis, VVCR values range from 0.5 to 1.0, with the optimal ratio being 0.5 to 0.7 . VVCR issumption . The autCMR data . Soon afapproach . Althougm were higher among the non-reactive subjects. The median WHO-FC was also higher in this group. These parameters indicate a more severe disease status among the non-reactive children and thus, points to movement towards an uncoupled state. The non-reactive group is also significantly older with a trend towards having PH diagnosis for a longer time period, reflecting the progressive nature of PH. The slope of the line for the reactive patients is smaller than for non-reactive. This suggests that RV functional reserve is relatively preserved. Therefore, these children are able to accommodate an increase in afterload. However, the large slope in the non-reactive patients suggests that they are in the maladaptive remodeling phase and can no longer accommodate an increase in afterload. Future studies of the pediatric population and breakdown of etiologies will enhance the understanding of PH phenotypes.In our study, the differences between the reactive and non-reactive subjects are significant. Not surprisingly, the PVRi trended towards higher values, and the RVEDVi and VVCRm is related to RV ejection fraction [VVCRfraction , which hfraction , 23, 24.m. Moving forward, this factor must be teased out in order to understand the impact of tricuspid regurgitation in the progression of PH. The subject group in this study is small and is a significant limitation to the interpretation of this data. The data presented here is a preliminary look at the feasibility of using CMR in estimating VVCR in children with PH and to compare this approach to a more standard approach using cardiac catheterization. A larger subject population with data collected from multiple pediatric centers would be required to achieve adequate power. That, however, does not negate the importance of the findings in this study and is the stepping stone to posing the question for clinicians: can serial catheterization in children with PH be avoided if non-invasive imaging can provide adequate cardiovascular data for the management of these patients? And if so, this can potentially open the door for facilitating research in a vulnerable population that is unique from the adult population in whom the majority of PH research has been done.Limitations of this study include those inherent to a retrospective study. While the separation of 14 days between cardiac catheterization and CMR is longer than ideal, the infrequency of these two procedures being performed during a close time period for clinical care necessitated expanding our time frame; albeit 15/17 of the subjects had the procedures performed within 48 h of one another. We also recognize that the same patient may have had the cardiac catheterization performed under anesthesia while being awake for the CMR, which potentially can change the hemodynamic state. However, this is unavoidable since most pediatric catheterization at our institution is performed under general anesthesia. Anesthesia, on the other hand, is avoided for CMR if possible for children over the age of 8 years and may be a better reflection of the cardiovascular function of the subject at baseline. Two of the subjects had greater than mild tricuspid regurgitation. The additional volume from the tricuspid regurgitation would impact the RVEDVi, and thus, also impact the VVCRMeasurement of VVCR by noninvasive means in pediatrics is feasible. Pulmonary vascular non-reactivity may contribute to ventricular-vascular decoupling in severe PH. Therapeutic intervention to maintain a low vascular afterload in reactive patients, may preserve right ventricular functional reserve and delay the onset of RV-PA decoupling. Use of VVCR may have significant prognostic implication.


Anemia is present in about 40% of heart failure (HF) patients. Iron deficiency (ID) is present in about 60% of the patients with anemia  and in about 40% of patients without anemia . Thus ID is present in about half the patients with HF. The ID in HF is associated with reduced iron stores in the bone marrow and the heart. ID is an independent risk factor for severity and worsening of the HF. Correction of ID with intravenous (IV) iron usually corrects both the anemia and the ID. Currently used IV iron preparations are very safe and effective in treating the ID in HF whereas little information is available on the effectiveness of oral iron. In HF IV iron correction of ID is associated with improvement in functional status, exercise capacity, quality of life and, in some studies, improvement in rate of hospitalization for HF, cardiac structure and function, and renal function. Large long-term adequately-controlled intervention studies are needed to clarify the effect of IV iron in HF. Several heart associations suggest that ID should be routinely sought for in all HF patients and corrected if present. In this paper we present our approach to diagnosis and treatment of iron deficiency in heart failure. The role of iron deficiency (ID) in heart failure (HF) has been the subject of many recent reviews over the last 2 years ,5,6,7,8.The presence of ID in HF has been confirmed in studies showing reduced iron content in the bone marrow  and in tBut these associations between morbidity and mortality in HF and ID may not be causal. To prove that ID is actually causing damage one must treat the ID and see the response of the HF patient. Although no long term studies have been published that have shown that treatment of ID can improve HF, five placebo-controlled randomized studies using intravenous (IV) iron ,23,24,25In these studies the treatment with IV iron has been shown to improve the anemia ,26,27,28The QoL parameters that are improved include reduced physical limitation, improved mobility, improved self care, increased daily activities, and reduced general pain, discomfort, anxiety and depression ,29.The IV iron treatment also improved renal function in several studies ,23,25,35ID correction also reduced several prognostic markers associated with worsening of HF including levels of C-reactive protein ,25, betaThe correction of ID also reduced admissions for HF in some studies ,24. WhenAlthough the anemia is also improved with the IV iron therapy, the improvements in HF have been shown to be independent of the improvement in anemia ,23,24,25The European  and the Despite such guidelines we recently found that only 19.7% of patients admitted to our hospital with a primary diagnosis of HF had their iron parameters measured, yet in those in whom it was measured, 80% were found to be iron deficient ,44. A si(1)Reduced iron intake due to low protein diets and anorexia;(2)Gastrointestinal blood loss due to uremia, gastritis, tumors, platelet inhibitors, anticoagulants and phosphate binders . In addition HF itself can cause reduced iron absorption due to intestinal cell dysfunction due to bowel edema and other causes;(3)Erythropoietin (EPO) used for the treatment of anemia uses up iron to form Hb, and this eventually will cause ID;(4)Inflammation.There are many causes of ID in Renal Failure (RF) and HF ,4,5,6,7,(4.1)Reduced EPO production in the kidney leading to inappropriately low EPO levels in the blood for the degree of anemia present;(4.2)Reduced erythropoietic response of the bone marrow to Erythropoiesis Stimulating agents (ESA);(4.3)Hepcidin-induced failure of iron absorption from the gut;(4.4)Hepcidin-induced trapping of iron in iron stores in the macrophages and hepatocytes preventing the release of iron into the blood.Both RF and HF are inflammatory conditions cause increased cytokines, and this can cause anemia and ID. These cytokines include Tumor Necrosis Factor-α (TNFα) and interleukin-6 (IL-6). They can cause four hematological abnormalities:The latter two abnormalities listed above have been reported to cause ID.Hepcidin is a protein released from the liver by IL-6. It inhibits the protein ferroportin, which is found in the gastrointestinal tract and in macrophages and hepatocytes and is responsible for the release of iron from these three types of cells into the blood. Therefore, if ferroportin is inhibited, gastrointestinal iron absorption is diminished, and iron also is not released from its storage in macrophages and hepatocytes. This results in decreased levels of iron in the blood which leads to decreased delivery of iron to the bone marrow and, therefore, ID anemia, even in the presence of adequate total iron stores . Because hepcidin is filtered and removed in the kidney, its levels increase even further in Renal Failure (RF) which can also partly explain the ID in this condition . About hThere are hundreds of enzymes in the body that depend on iron for their function . Iron isDespite the positive studies of IV iron in HF and RF there are no long-term controlled studies that have been done on the use of IV iron in HF patients and there is concern about the safety of such preparations ,50 ExcesIron deficiency in animal studies has shown the development of left ventricular hypertrophy and dilatation, mitochondrial swelling, disruption of sarcomeres and release of reactive oxygen species that can cause cell damage .2) only in the IV iron group. However the study was underpowered with only 18 patients completing it. In a retrospective study of 105 patients with HF with systolic dysfunction oral iron supplementation improved iron stores and anemia similarly to previously reported results with intravenous iron therapy suggesting that oral iron therapy may be useful. But, as stated this study was retrospective [2 [In most studies comparing oral to IV iron in RF, IV iron has been found to produce a greater and more rapid Hb response than oral iron with fewer side effects, and many patients can reach a target Hb of 11.0–11.5 g/dL with IV therapy alone, and therefore avoid the use of Erythropoiesis Stimulating Agents (ESA) altogether ,60. In aspective . Much moctive [2  This uncctive [2 . ClearlyIn patients with ID who had anemia without known heart disease and arrythmias and who were treated with oral iron until the anemia was corrected, echocardiography was performed before and after treatment. At baseline there was an increase in Left Ventricular Diameter (LVD), Left Ventricular Mass index (LVMI), Left Atrial Volume Index (LAVI), and increased LV filling pressure. The follow up results, similar to the findings in the HF studies mentioned above, showed that those treated with IV iron had significant decreases in LV end-diastolic and end-systolic diameters and LV Mass index. In addition there was evidence of decreased LV filling pressure . Thus orID is one of the most common conditions in the world. It may appear with anemia but more often is present for many years before anemia develops. In addition its correction has been found to improve many other conditions including: chronic kidney disease (CKD) ,67,68, iThere are many conditions in which the prevalence of ID is increased but no adequate studies of iron administration have been performed to assess their effect on ID, anemia and patient performance. These include: heart and kidney transplantation , obesityOne reason for the increased risk of stroke, coronary artery disease, thromboembolism and peripheral vascular disease seen with ID could be the thrombocytosis and increased platelet aggregation caused by the ID ,91,101.To diagnose ID in HF and other conditions one would have to measure the iron parameters serum iron, serum transferrin, %Transferrin Saturation (%TSat), and serum ferritin ,117,118 There is no test that can predict very accurately the degree of response to IV iron in HF or RF or in other inflammatory conditions with great accuracy ,117,118.There currently are no generally agreed upon guidelines as to when to start or stop treatment for IV iron in HF. Many studies have recently used either a serum ferritin of <100 µg/L or a serum ferritin of 100–300 µg/L associated with a %TSat <20% in HF. According to the Clinical Renal Guidelines for Iron Deficiency Treatment in Renal Failure ,67, IV iDeficiencies in Vitamin B12 and Folic Acid may each be found in about 5% of the HF patients and should be routinely sought for and treated .Non anemic iron deficiency is very common ,122. It p = 0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the Darbepoetin alfa group and 114 patients (10.0%) in the placebo group (p = 0.01). There was no difference in renal function or progression of renal disease in the treated and untreated group. Cancer-related adverse events were similar in the two study group. The overall findings did not support the use of Darbepoetin alfa in these patients. Thus a positive role for ESA in HF has not been proven [A large study of Erythropoiesis Stimulating Agents (ESA) in HF has recently been published, the Reduction of Events with Darbepoetin alfa in Heart Failure (RED-HF) study, which was undertaken in 2006 and recently completed ,124. Then proven . We feel(1)All patients with heart failure should routinely have a serum iron, serum Transferrin, % Transferrin Saturation and serum ferritin performed in addition to the usual blood work irrespective of whether anemia is present or not.(2)IV Iron therapy can be given to heart failure patients with serum ferritin <100 µg/L or serum ferritin 100–300 µg/L with %TSat <20% until either a %TSat of 30% or a serum ferritin of 500 µg/L has been reached.(3)Current IV iron preparations are all quite safe and can be used with the exception of High Molecular Weight Dextran which should not be used because of it allergic potential.(4)If the clinical situation is not acute, unstable, or symptomatic, oral iron can perhaps be used but if the patient is unstable or symptomatic then consideration should be given to a course of IV iron which corrects both the ID and anemia more rapidly, to a greater degree and in a higher percentage of patients than oral iron therapy and more completely corrects the ID.(5)Erythropoietin injections should only be used once ID has been corrected and the Hb is still <10 g/dL. If erythropoietin agents are used they should only be used in low doses because of the dangers of thromboembolic phenomena and hypertension associated with high doses of ESA.(6)The target Hb for heart failure is usually accepted to be around 11.5 g/dL.(7)Treatment of heart failure with IV iron may prevent the progression of the renal disease as well as the heart disease.(8)Secondary causes of worsening heart failure and renal failure such as Non Steroidal Anti Inflammatory Drugs (NSAIDs), hypotension, urinary retention and excessive salt intake should be routinely looked for.(9)Preoperative correction of ID with IV iron may prevent transfusions and their associated cardiovascular complications in the postoperative period.(10)Vitamin B12 and folic acid levels should be measured in all HF patients and deficiencies treated.(11)The cause of ID should be looked for when ID is found.Our personal approach based on the current data isThere are still many uncertainties about whether to begin with IV iron or oral iron in HF: (1) The lack of a long-term double- blind placebo-controlled studies of a size adequate to assess morbidity and mortality is a major problem for both the IV and oral iron treatment in HF; (2) Doctors should be made more aware that ID can be present and cause serious signs and symptoms even when no anemia is present; (3) More data on safety of the IV iron preparations in HF is needed (4) Do hospitalization rate and mortality really improve in HF with IV iron therapy? (5) Does cardiac function really improve in HF with IV iron therapy? (6) Does renal function really improve in HF with the IV iron therapy? (7) Better parameters are needed to assess iron deficiency. Should Hepcidin, transferrin receptor protein, % hypochromic red cells and/or reticulocyte Hb concentration become routine tests in the search for ID? (8) Is there a role for oral iron therapy in the treatment of ID of HF? (9) Does the same IV iron therapy work in diastolic heart failure with a normal ejection fraction as it does in systolic heart failure? (10) Is ID really more common in the elderly, obesity, diabetes, metabolic syndrome, coronary heart disease, acute myocardial infarction, peripheral vascular disease, stroke, thromboembolic diseases, COPD, asthma and rheumatoid arthritis? If so is there a role for correction of ID in these conditions?


Treatment with the intraaortic balloon pump (IABP) is the most common form of mechanical support for the failing heart. Augmentation of diastolic pressure during balloon inflation contributes to the coronary circulation and the presystolic deflation of the balloon reduces the resistance to systolic output. Consequently, the myocardial work is reduced. The overall effect of the IABP therapy is an increase in the myocardial oxygen supply/demand ratio and thus in endocardial viability.This is an overall synopsis of what we need to know regarding IABP. Furthermore, this review article attempts to systematically delineate the pathophysiology linked with the hemodynamic consequences of IABP therapy. The authors also look at the future of the use of the balloon pump and conclude that the positive multi-systemic hemodynamic regulation during IABP treatment should further justify its use. Different forms of support of the failing heart consist of Cardiopulmonary Bypass Pumps/ ECMOs, internal or external Counterpulsation and the various modes of Auxiliary heart pump.Intraaortic balloon pump (IABP) is a form of internal counterpulsation, acting as an assisting circulatory support device. Diastolic augmentation during inflation potentially contributes to coronary, cerebral, and systemic circulation.According to Freedman et al.  presystoPrimarily the impact of IABP is to increase the myocardial oxygen supply demand ratio. The effectiveness of Intraaortic balloon counterpulsation on improving oxygen supply and subsequently left ventricular subendocardial blood flow would be best appreciated by examining the endocardial viability ratio  in a latThe possibility to alter timing of pressure events during a heartbeat was conceived by Kantrovitz et al. . ExternaSimultaneously other researchers –6 experiPreliminary studies with an intraaortic balloon pump took place in 1961 by S. Moulopoulos and associates . Latex tThe concept of external counter pulsation was introduced by Dennis et al.  in 1963.The first clinical application of a successful treatment with IABP was reported in 1967. Intra aortic balloon pumping was advocated successfully in a 45 year old female who had sustained a myocardial infarction and was hypotensive, comatose and anuric in severe cardiogenic shock.By the early 1970s and after a series of successfully treated patients with cardiogenic shock (The Kantrowitz-team had treated 30 patients) the IABP had been convincingly promised to be helpful in acute low cardiac output state following left ventricular failure.Buckley et al.  looked aMundth and co-workers  reportedJacobey et al.  followinIn 1971 Feola and associates  looked uKrakauer et al.  in the bIn 1972 Bregman and coworkers  developeThe development of catheters and balloons of polyurethane material enable prolonged periods of counterpulsation.In 1973 two different groups , 16 repoBy 1976 more than 5000 patients with post-cardiotomy low cardiac output had received IABP treatment in United States.Continuous evolution brought a method of insertion of the balloon catheter percutaneously without the need for surgical cut down , 18. InvDuring the past decade major mechanical and engineering developments have allowed optimal timing of counterpulsation and on-line monitoring of blood pressure and cardiac output.A cylinder of gas source .A valve unit, which allows delivery of the gas.A monitor system for acquisition of electrocardiogram and arterial blood pressure.Control unit which processes the electrocardiogram and develops a trigger signal; this is used for timing of balloon inflation and deflation by activating the valve unit and allowing either opening of the valve in order to deliver the gas, or closure of the valve unit in order to stop the gas flow.The IABP console delivers a specific volume of gas through a pneumatic system into a balloon during a predetermined time interval followed by retrieval of the gas, Fig. . The conBoth Helium and Carbon dioxide have been used as driving gases, however the use of helium has theoretical advantages according to Hendrickx et al. : These iThe size of the aorta is related to patient size, age and weight.The ideal balloon for any patient has to have the length from the left Subclavian artery to the coeliac artery take off, the inflated diameter 90 to 95 % of that of the discending aorta and has to be equal in volume to the volume of blood in the aorta at any given time. The latter statement confirmed by Kantrowitz and colleaques who stated that the balloon is limited by the volume of blood contained within the aorta just prior to inflation . Further increases in pumping volume result only in distention of the aorta (due to aortic elasticity) and not in the effective pumping of the balloon.IABC usage for adult patients has mainly been limited (82 % of the cases) to the use of 40 cc balloon, with membrane length (non tapered section plus tapered ends) varying between different manufacturer from 22 to 27.5 cm and inflated diameter between 15 to 18 mm, Table While in many clinical situations volume of 40 cc are appropriate, it should be said that too large IAB increases vascular morbidity whereas too small IAB reduces the cardiac benefit. 50 cc Balloon has been used in taller patients.Diastolic augmentation is maximized when stroke volume is equal to balloon volume. If stroke volume is very low (ie 25–30 ml) or very high (95–100 ml) augmentation will be decreased.The closer the balloon is to the aortic valve, the greater the diastolic pressure elevation. It is obvious that local anatomical factors limit the position of the balloon within the aortic arch therefore the optimal balloon position will be that where the tip is situated distal to the left Subclavian artery take off. The proximal balloon end should be lying above the renal vessels. Incorrect balloon position results in reduced diastolic augmentation or vascular morbidity due to direct intimal injury or plaque distortion and embolization or finally direct occlusion of the arterial lumen.Cardiac Index < 1.8lt/minSystolic arterial pressure < 90 mmHgLA or RA pressure > 20 mmHgUO < 20 ml/hSVR > 2100Metabolic acidosisDespite adequate preload, max pharmacological support and IAB pumping:Severe Peripheral Vascular diseaseInfectionHepatic diseaseCancer with metastasisSevere Coagulopathy“Relative” Exclusion criteriaFollowing the principle of counterpulsation, the IAB is deflated during systole which coincides with QRS –T interval . In this manner balloon inflation during cardiac systole is prevented. The IAB is inflated during diastole, which coincides with T-P interval, Fig. Cardiovascular consequences are mainly due to the effect on preload and afterload . BalloonIntraaortic balloon counterpulsation is instituted by insertion of a catheter mounted with a distensible polyurethane balloon in the patients descending aorta. Helium gas is shuttled from the balloon pump console. Inflation occurs immediately upon onset of diastole. Deflation occurs during isometric contraction. In a mechanical sense balloon inflation causes volume displacement. Total or regional blood flow is potentially improved with counterpulsation. Coronary circulation and perfusion to the aortic arch trifurcated vessels is potentially increased. Balloon inflation augments the intrinsic Windkessel effect, which augments peripheral perfusion . At the With proper timing if one compares the systolic pressures of non-assisted beats with systolic pressures following IABP assist one would conclude that intra-aortic balloon pumping results in a decline in systolic pressure by up to 10 % , 26. A dDuring IABP end diastolic aortic pressure is decreased up to 30 %; indicating systolic unloading.The Aortic valve during balloon pumping opens early therefore the isometric phase of LV contraction is decreased. This time interval is proportionally related to myocardial oxygen consumption .According to Urschel and collegues  the peakThere is an increase in LV Ejection Fraction during IABP . LikewisThe Starlings law curve for the left ventricle is affected by IABP . There iThe left ventricular diastolic volume is decreased due to systolic unloading.The relation between left ventricular diastolic pressure change and left ventricular diastolic volume change (LV stiffness) exhibits a trend towards reduced values , a fact The IABP effect on improving myocardial oxygen supply could be better understood by examining the diastolic pressure time index (DPTI) and tension time index (TTI), Fig. DPTI reflects diastolic and subendocardial blood flow and depends on aortic diastolic pressure, left ventricular end diastolic pressure and diastolic duration. DPTI increases with IABP due to an increase in diastolic blood pressure and a decrease in end diastolic pressure.The area under the left ventricular systolic pressure curve, which reflects myocardial oxygen demand, is termed tension time index (TTI). TTI decreases with balloon deflation due to a decrease in systolic blood pressure.The ratio DPTI/TTI reflects the relation between oxygen supply and consumption of the myocardium representing the Endocardial Viability Ratio (EVR). A value of 1.0 or higher signifies a normal supply/demand balance. An EVR of less than 0.7 indicates severe myocardial ischaemiaPhillips et al.  introducBolooki et al.  states tIt has to be clarified that TTI as an index of oxygen demand only accounts for pressure; on the other hand myocardial oxygen consumption is a function of force that is proportional to both pressure and volume, therefore although EVR will only reflect the decrease in pressure IABC produces a decrease in volume as well as pressure. As a consequence the decrease in myocardial oxygen consumption will be underestimated.Balloon inflation displaces blood proximally increasing coronary perfusion by also increasing diastolic pressure and the diastolic perfusion gradient , 38.There are various animal studies that assessed the contribution of the intra aortic balloon on myocardial perfusion. Results were variable. Kern et al.  stated tGewirtz et al.  undertooMcDonald et al.  found thHowever Folland and associates  contradiFreedman and associates  called mDuring counterpulsation aortic end diastolic pressure is lowered. Applying Laplaces low, lowering of aortic end diastolic pressure during static work  will decrease the amount of tension generated at the time the aortic valve opens. Therefore reducing myocardial oxygen consumption.Akyurekli et al.  undertooPeripheral blood flow is determined by pressure, resistance, length and viscosity. Balloon inflation during diastole increases the arterial pressure, which increases the arterial-venous gradient and thus improves flow. In addition balloon inflation in diastole displaces stroke volume and thus activation of the aortic baroreceptors inhibits the medullary vasoconstrictor reflex. Peripheral resistance decreases, which, as demonstrated by Poiseuilles low improves blood flow.The impact of IABC on splachnic blood flow has also been studied. Landreneau et al.  studied The effects of IABP upon postoperative renal function, was studied by Ahmed et al. ; they shSwartz et al.  studied Balloon position: The closer to the Aortic valve the greater the diastolic pressure elevation.Balloon Volume: When the balloon volume is equal to the stroke volume the diastolic augmentation is maximized.Balloon diameter and occlusivity: The greatest augmentation occurs with complete aortic occlusion.Balloon Configuration/Driving gas & Timing.Stroke volume: If stroke volume is less than 25 ml little diastolic augmentation can be expected.Arterial pressure: The significance of aortic elasticity is illustrated by the fact that aortic volume doubles between a mean arterial pressure of 30 mmHg and a normal mean pressure of 90 mmHg. Our group  calculatThis paper is worth mentioned because it outlines the variables that influence diastolic pressure augmentation during balloon inflation . The varThe incidence of IABP treatment following Cardiac surgery is reported to be around 7 % in various units. This of course is dependent on the case mix and stratifying patients according to the Euroscore, one would obviously suggest that IABP usage correlates with ascending scoring.According to various reports, Poor LV function, History of Myocardial Infarction, Female sex, Diabetes mellitus, Peripheral Vascular Disease and also Left Main Stem Disease are incremental risk factors for IABP utilization.The unique physiological balance of benefits of IABP, include support of the coronary circulation , 53, as Temporary support of the left ventricular function due to cardiac failure, due to myocardial infarction or due to intraoperative injury.Improvement in the oxygen supply/demand balance to decrease the extent of the ischaemic zone and to preserve myocardial viability.The indications for use of an IABP involve two areas:However the efficacy of IABP is dependent upon the phase of myocardial ischaemia or the time elapsed from initiation of myocardial infarction as well as the stage of left ventricular function.Triple Vessel disease with moderately preserved left ventricular function and good distal targets.Significant mechanical lesions such as mitral insufficiency or ischaemic ventricular septal defect.The value of the balloon pump as a circulatory assist device in the treatment of cardiogenic shock is well established –57. SingVarious clinicians must agree that during ischaemic episodes there is a potential window of opportunity were adequate hemodynamic support would ensure that adequate myocardium would remain viable to allow resumption of function, following coronary artery bypass grafting , 60. ThiGold and associates  showed tIn unstable patients especially in the presence of left ventricular dysfunction, the use of IABP allows safe performance of diagnostic studies followed by surgical intervention. Zhang et al.  agree thLangou and associates  report iAlthough the majority are not controlled non-matched series, they however still indicate that patients who are refractory to maximal medical therapy can be operated on with IABP stabilization with a low operative mortality and a low peri-operative infarction rate , 66. IncIn Theory, IABP could be used during acute myocardial infarction in order to decrease the size of the infarct, to support the cardiac function, to prevent infarct extension and to reduce complications associated with the event.Miller and associates  publishen = 12 patients) experienced ischaemic pain. Ischaemic pain was not persistent in the second group (n = 14 patients). With institution of IABP more pronounced hemodynamic improvement exhibited in-group I.O Rourke et al. examined the effects of IABP on 26 patients with post acute myocardial infarction heart failure. The first group  of a major branch of the left coronary artery due to percutaneous intervention would benefit from IABP followed by emergency revascularization , 72.In patients with acute myocardial ischaemia when tachyarrhythmia is refractory to second or third line antiarrhythmic therapy IABP treatment should be instituted  followedAlmost all the ventricular dysrhythmias due to ischaemia are temporarily controllable with medication; therefore few patients would require IABP prior to a revascularization procedure. There is, however a role for using IABP in patients who have an unstable rhythm due to myocardial infarction early after myocardial revascularization.Patients with ventricular aneurysms and arrhythmias with triple vessel disease amenable to bypass grafting have shown good survival results, however arrhythmia has persisted in 30 % of the cases  unless sMost frequently involves the posterior papillary muscle and the responsible coronary artery by 80 % is the right coronary artery. According to Chen et al.  early moIABP should be used in patients who have slipped into cardiogenic shock following post-infarction MR. This would allow haemodynamic stability in order to permit left ventricular catheter studies to be followed by mitral valve replacement. Concomitant bypass improves early and late survival , 79.In the majority of cases with cardiogenic shock pulmonary congestion ensues . AccordiPoulsen et al.  reportedIABP treatment during ischaemic rupture of the ventricular septum, increases the mean aortic pressure and cardiac output and decreases the right ventricular and pulmonary wedge pressure.Patients should be operated upon as quickly as possible and a delay in surgery can lead to multi-systemic organ failure. These patients are at high risk for operative mortality and even with prompt surgical management, operative mortality remains significant because of heart failure and risk of fatal haemorrhage according to Sharma et al. .Agnihotri and colleagues’ meta-analysis of 17 series from 1991 to 2009 reported five-year survival rates ranging from 33 % to 65 % especially if concomitant revascularization procedure had been advocated , 85.The incidence of utilization of IABP in the course of cardiac catheterisation is reported by the International Benchmark Registry to be as high as 1 in 5 as an adjunct to high-risk PCI.Various authorities around the world  have adoMulti-vessel angioplasty in-patient with hypotension,Angioplasty of the only functional coronary arteryLeft main coronary artery angioplasty unprotected by a patent graft.Relative criteria have been developed for selection of patients who should be considered for prophylactic IABP before PCI:IABP mainly reduces the afterload thus improving the performance of the failing heart. In a series among 274 heart transplant patients, thirty-seven (28 %) required IABP as a bridge to transplantation.Two patients presented by Masaki et al. who underwent intraperitoneal surgery under the support of intraaortic balloon pump (IABP). In one patient, the IABP was inserted urgently because of the development of chest pain with significant ST depression on arrival in the operating room .The small size of the aorta.High elasticity of the aorta, which precludes effective balloon pumping.Small stroke volume, which precludes balloon augmentation.The major problems encountered here are:Pollack et al.  reportedIn theory would be indicated for patients with pulmonary hypertension such as after embolectomy or mitral valve replacement. Acute infarction involving the right ventricle would be a relative indication. Despite the obvious theoretical advantages, in reality the results are equivocal .Combination of IABP with external compression during resuscitation theoretically improves coronary and cerebral perfusion.Patients with severe left ventricular muscle dysfunction and low ejection fraction who need an extensive operative procedure, which does not improve the cardiac performance immediately.Patients requiring reoperations (redo-grafts) while they are suffering from an acute left ventricular dysfunction due to an unstable coronary syndrome.When the ejection fraction in percent is lower than the end-diastolic pressure in mmHg.Patients with severe long standing aortic stenosis and compromised ejection fraction especially when there is a need for associated procedures such as aortic root enlargement or coronary artery bypass grafting.Patients with severe ischaemic mitral incompetence and dilated poor left ventricular function.Patients with large left ventricular aneurysms and low ejection fraction.Patients with left main stem coronary disease and an acute myocardial infarction in progress.Post-operative right ventricular dysfunction.As early as the beginning of 1970s Berger et al.  and alsoEmergency use of IABP after cardiac surgery should be considered, when: all the causes of incomplete revascularization have been eliminated & there is a difficulty to wean from heart lung machine after attempting for 30 min at flow rates above 500 ml/min, with hypotension and low cardiac index despite increasing requirements of inotropic support (Dopamine > 10 mcg/Kg/min).Utilization of IABP as an emergency measure for postoperative cardiac failure has consistently produced a survival rate of around 70 % by various groups such as Pennington et al. . A 2010 IABP complications are resulted during difficult insertion and malposition, prolong IABP stay and due to patient’s comorbidity such as peripheral vascular disease, small size patients, use of sheath of IABP and Diabetes.A paper by Rastan et al.  identifiInjuries resulting during IABP action could be overlooked unless catastrophic clinical implications are encountered; an important paper by Isner et al.  reviewedBy enlarge, complications are reported to be primarily associated with the insertion process and prolonged balloon pumping, rather than removal or post removal monitoring.Obviously, due to the nature of the IABP, the main complications relate to vascular injury, with studies suggesting vascular ischaemic complications of between 8–18 % with major limb ischaemia reported to be less than 1 % –102.n = 18 pt) or with thrombectomy . One patient developed gangrene and required amputation.In a study published by our group , cold puThrombocytopenia, defined as platelets <150,000/mL or >50 % decrease from baseline, occurred in 57.9 % of patients.Among patients undergoing IABP, thrombocytopenia is generally mild, appears to be unrelated to concomitant heparin use, and is not associated with an increased risk of major bleeding or in-hospital death , 105.Rupture of the IABP is rare but can cause gas embolism and potential entrapment of the balloon within the arterial tree. This was first reported by Rajani et al.  however Finally, Complications of thrombosis and infection are related to the duration of IABP therapy while the limb ischemic problems are more a function of the atherosclerotic status of the common femoral artery and either the ratio of balloon catheter diameter to arterial lumen, or the difficulty of dealing with a severely atherosclerotic artery with loose plaques or fragility requiring excessive surgical manipulation.To summarise, the use of the IABP is justified because an increase in diastolic pressure during balloon inflation augments the coronary circulation. Further, pre-systolic deflation of the balloon reduces the resistance to systolic output; thusa decrease in myocardial work.The efficacy of the IABP is reflected by the positive outcomes of the high number of patients who are weaned from the device. The success rate is higher for patients, in whom the device is deployed early, reflecting the reversible nature of ischaemic pathology and the positive contribution of the IABP to preventing the cascade of complications of ischaemic heart disease.Mechanical assistance to the circulation is a rapidly developing field. The concept of intervention within the cardiac cycle in order to improve cardiac performance has been studied from every angle. Diastolic counterpulsation by means of IABP is the direct application however various manipulations in the systolic phase have been suggested by different researchers.A Spherical balloon introduced into the ascending aorta with the diameter equal to that of the aorta and inflated for 80 msec during the middle third of the ejection phase with main effect to increase the coronary flow.A small balloon introduced into the LV and inflated for 100 msec during late systole, thus reducing LV residual volume after cardiac systole and increases LV capacity for the next contraction. The result may be an increase in contractility and stroke volume. By inflating the balloon at the end of diastole the LV end diastolic pressure increases resulting in improvement of the stroke volume.Future developments most likely would involve better definition of the subgroup of patients requiring IABP support, clear criteria for weaning and improvement in catheter technology and in drive consoles.DPTI, diastolic pressure time index; ECMO, extracorporeal membrane oxygenation; EVR, endocardial viability ratio; IABC, intra-aortic balloon counterpulsation; IABP, intra-aortic balloon pump; LVEDP, left ventricle end-diastolic pressure; PCI, percutaneous coronary intervention; TTI, tension time index; VAD, ventricular assisted device


The presence of myocardial late gadolinium enhancement (LGE) in patients with sarcoidosis is a powerful predictor of major adverse events . In this study, we aim to determine if the burden of LGE, left ventricular (LV) and right ventricular (RV) end-diastolic and end-systolic volume index (EDVi & ESVi) and ejection fraction (EF) can be used to improve risk stratification in patients with cardiac sarcoidosis (CS).We identified 25 consecutive subjects with a diagnosis of CS (biopsy-proven extra-cardiac sarcoidosis and presence of LGE on cardiovascular magnetic resonance). Imaging was performed on a 1.5T scanner. Short axis cines  spanning the entire LV were acquired to determine LV and RV volumes. Short axis slices were also obtained 10 minutes after contrast (gadodiamide 0.15 mmol/kg) using a phase sensitive inversion recovery reconstruction. LGE was identified on each slice as regions with signal intensity (SI) > 5 standard deviations above the mean SI of normal remote myocardium. The total amount of LGE as a percentage of LV mass (%LGE) was determined using Diagnosoft Virtue software  were female. Mean follow up was 39 ± 15 months. Six (24%) of patients had MAE. There was a significant difference in %LGE, RVEF and RVESVi but not LVEF, LVESVi, LVEDVi or RVEDVi between those who had MAE and those who did not (Table The burden of LGE and RV size and function (not LV size and function) further improve prediction of death and significant ventricular arrhythmia in patients with cardiac sarcoidosisNone.


Bicuspid pulmonary valves and pulmonary artery aneurysms are two rare entities, reported in association, and usually attributed to hemodynamic alterations caused by the bicuspid pulmonary valve. We present magnetic resonance images of a patient with a bicuspid pulmonary valve and pulmonary artery aneurysm, and propose an alternative mechanism for this association, based on recent embryologic studies that link anomalies of the semilunar valves and great vessels with derangement of the cardiac neural crest cell development. Bicuspid pulmonary valves are rare. A study of 3,861 donor hearts, dissected at the European Homograft Bank revealed only four cases (0.1%) of bicuspid pulmonary valves . Bicuspi1 × VTI1 = Area2 × Peak VTI2) [peak = 4Vpeak2).A 59-year-old female with history of an abnormal pulmonary valve volunteered for a routine cardiovascular magnetic resonance (CMR) exam. She was completely asymptomatic and took no medications. She was employed and stated that she had no limitations regarding her exercise capacity. There was no family history of congenital heart disease. CMR was performed in a 1.5 T Philips Achieva whole body MR scanner using a five-element phased-array receive coil . Breath-hold, balanced steady-state free precession (b-SSFP) cine images were obtained in the vertical long axis, horizontal long axis, left ventricular outflow tract and left ventricular short axis planes. Breath-hold flow quantitation images  in planes parallel to the pulmonary valve plane were obtained at the valve level, 1.5 cm above the valve and 1.5 cm below the valve. Images were analyzed using a ViewForum workstation . Left ventricular ejection fraction was calculated from the short axis images, using Simpson’s rule, excluding the trabeculae and papillary muscles. From the velocity-encoded images, the pulmonary valve area was calculated by planimetry and by applying the continuity equation as previously described (Areaak VTI2) . Peak pr2 by planimetry, and 2.1 cm2 using the continuity equation. The calculated peak pressure gradient across the pulmonary valve was 13.5 mm Hg. For video supplementary files, see www.cardiologyres.org.CMR revealed normal right ventricular and left ventricular function, normal aortic valve, bicuspid pulmonary valve and aneurysmal dilatation of the pulmonary artery trunk with a diameter of 3.9 cm , 2. The Given our patient’s mild degree of pulmonary valve stenosis, it is possible that her pulmonary artery aneurysm is not secondary to hemodynamic alterations attributable to her bicuspid pulmonary valve, but that her bicuspid pulmonary valve and pulmonary artery aneurysm may be both secondary to alterations in her normal cardiac neural crest cell development.


Background. Spasticity of the legs is common in multiple sclerosis (MS), but there has been limited research examining its association with ambulatory outcomes. Objective. This study examined spasticity of the legs and its association with multiple measures of ambulation in persons with MS. Methods. The sample included 84 patients with MS. Spasticity of the legs was measured using a 5-point rating scale ranging between 0  and 4 (contracted). Patients completed the 6-minute walk (6 MW), timed 25 foot walk (T25FW), and timed up-and-go (TUG), and O2 cost of walking was measured during the 6 MW. The patients undertook two walking trials on a GAITRite  for measuring spatial and temporal parameters of gait. The patients completed the Multiple Sclerosis Walking Scale-12 (MSWS-12) and wore an accelerometer over a seven-day period. Results. 52% (n = 44) of the sample presented with spasticity of the legs. Those with leg spasticity had significantly worse ambulation as measured by 6 MW , T25FW , TUG , MSWS-12 , O2 cost of walking , average steps/day , and walking velocity  and cadence . Conclusion. Leg spasticity was associated with impairments in ambulation, including alterations in spatiotemporal parameters and free-living walking. Data from the Patient Registry of the North American Research Committee on Multiple Sclerosis indicated that 84% of persons with MS reported spasticity . Spastic with MS . To dateWe further are unaware of research that has examined the associations among spasticity, spatial and temporal parameters of gait, and free-living ambulation in persons with MS. The evaluation of time and distance parameters during walking can be undertaken using an instrumented walkway , 5 and i2 cost of walking), and perceived (MSWS-12) measures of walking; the replication was important for confirming previous research in the context of the measures, particularly spasticity, and sample in the present study. We then extended previous research by examining the association between the presence of spasticity in the leg muscles and kinematic  as well as community (accelerometry) measures of walking. We further examined the association between severity of spasticity in the leg muscles and the comprehensive battery of walking outcomes. Consistent with previous research [This study involved a comprehensive examination of the association between spasticity of the leg muscles and walking outcomes in persons with MS. We first replicated and confirmed previous research by examining the association between the presence of spasticity in the leg muscles and performance , physiological . The sample primarily had a relapsing-remitting clinical course (n = 69 or 82% of cases) and the mean ± standard deviation disease duration was 11 ± 9 years. Of the 84 persons, 85% or 71 participants reported taking a disease-modifying therapy. The median Expanded Disability Status Scale (EDSS) [The sample consisted of 84 patients with a clinically definite diagnosis of MS who were recruited through the practices of three locally residing neurologists. The five criteria for inclusion were (a) capacity for independent ambulation or ambulation with an assistive device including cane, crutch, walking frame, or rollator walker; (b) age between 18 and 65 years; (c) willingness to undergo testing; (d) relapse free during the previous 30-day period before testing; and (e) absence of orthopedic and other neurological disorders; we did not screen for diabetic neuropathy or vestibular problems. The mean ± standard deviation age of the sample was 50 ± 10 years and the sample was predominantly female  , 12. TheThe TUG was performed in a patient room and on a carpeted floor with a clearly marked 10-foot distance from a stabilized chair. Participants were given standardized instructions, namely, to stand up from the chair without using arms to push off from the armrests of the chair, walk for 10 feet as fast and safely as possible, return to the chair, and sit down. The test has been validated previously for use in MS . The timThe MSWS-12 scale is a validated 12-item questionnaire designed to assess the perceived walking impairment in an individual with MS during the past two weeks . All the2 Cosmed, Italy). The O2 and CO2 analyzers of the portable metabolic unit were calibrated using verified concentrations of gases, and the flow-meter was calibrated using a 3-L syringe . Steady-state 2 cost of walking was expressed as mL·kg−1·m−1 by dividing steady-state −1·min−1 by actual walking speed in m·min−1 [ m·min−1 .−1), cadence (steps·min−1), base of support (cm), step time (sec), single leg support (% of gait cycle), double leg support (% of gait cycle), and swing phase (% of gait cycle). The average of the 2 trials for each variable was used in the analysis for improved reliability.Participants completed 2 walking trials along a 26-foot GAITRite  electronic walkway at a comfortable, self-selected pace as done in previous research involving persons with MS , 5. We r−1). There is evidence that accelerometers and the metric of steps·d−1 provide a valid and reliable measure of ambulatory physical activity in the community among persons with MS [The participants wore an Actigraph model GT3X accelerometer  on an elastic belt around the waist on the nondominant hip during the waking hours, except while showering, bathing, and swimming, for a 7-day period. Waking hours were defined as the duration from the point of waking out of bed in the morning until the point of going to bed in the evening. The participants were provided with a log sheet to record the time the accelerometer was worn and this was verified by checking the minute-by-minute accelerometer data. We summed the minute-by-minute step counts over each day and then averaged the values over the 7 days  and nonparametric  as well as chi-square statistics . This was followed by an examination of the distributions for data on all ambulatory outcomes based on estimation of skewness and kurtosis values. We then provided descriptive statistics including mean, median, standard deviation (SD), and range of scores for the ambulatory outcomes. We performed inferential statistics for the difference in the ambulatory outcomes between groups with and without leg spasticity by conducting independent samples t-tests; we performed nonparametric independent samples t-tests using Mann-Whitney U for confirming group differences for the t-test with outcomes that had nonnormal distributions. We opted for this approach as effect size estimates are derived from mean scores rather than medians and this would logically follow for a parametric analysis on means. The magnitude of group differences was estimated by calculating the Cohen's d effect size  [d of 0.2, 0.5, and 0.8 were interpreted as small, moderate, and large, respectively [2 cost of walking; spatial and temporal parameters of gait by the GAITRite; and average activity counts per day and step counts per day over 7 days by accelerometer. The alpha for statistical significance was set at 0.05. We did not adjust alpha for the multiple comparisons because of our directional hypotheses and replication of previous research. We further provided Spearman rank-order correlation coefficients (rs) for the association between spasticity severity and walking outcomes. Values for correlations of 0.1, 0.3, and 0.5 were interpreted as small, moderate, and large, respectively [The data analysis was conducted using SPSS version 18 . We initially compared the groups on demographic and clinical characteristics using independent samples viation) . Values ectively . The ambectively .n = 4 without leg spasticity and n = 12 with leg spasticity) and women (n = 36 without spasticity and n = 32 with spasticity) who had a clinically definite diagnosis of MS; there was a significantly larger percentage of men in the sample with leg spasticity . Relapsing-remitting MS was most common in those without leg spasticity (93% of cases) and those with leg spasticity (81% of cases); there was not a significant difference in MS type between groups . As would be expected, those with spasticity of the legs had significantly higher EDSS scores than those without spasticity ; this was driven by the Pyramidal , Cerebellar , Sensory , and Mental  Functional System scores. There were no statistically significant differences between groups in height, weight, or duration since MS onset, but the group with spasticity was significantly older than those without spasticity .The mean scores, standard deviations, ranges of scores, and the appropriate statistical test for the difference between the groups on demographic and clinical measures are provided in 2 cost of walking ; we provide both parametric and nonparametric t-tests in the text for those three variables when comparing groups of persons with and without spasticity. The mean (standard deviation) and median scores, ranges of scores, effect sizes for the ambulatory outcomes per group with and without leg spasticity are provided in The estimates of both skewness and kurtosis were less than 2.58  for all ambulatory and gait outcomes, with the exception of T25FW , TUG , and Ot = −3.93; P < 0.0001; Cohen's d = −0.86) in those with leg spasticity compared to those without leg spasticity. T25FW  and TUG  times were significantly longer for those with leg spasticity compared to those without leg spasticity. There were statistically significant and moderate associations between overall spasticity severity and 6 MW , T25FW , and TUG  performance; scatter plots for those associations are provided in 6 MW distance was significantly shorter  in those with leg spasticity compared to those without leg spasticity. There was a statistically significant and moderate association between overall spasticity scores and MSWS-12 scores .Perceived walking impairment based on MSWS-12 scores was significantly higher  in those with leg spasticity compared to those without leg spasticity. There was a statistically significant and moderate association between overall spasticity scores and O2 cost of walking .The energetic cost of walking was significantly higher  in those with leg spasticity compared to those without leg spasticity. There was a small, nonstatistically significant association between overall spasticity scores and steps·d−1 .Free-living ambulation based on steps·dt = −2.44; P < 0.05; Cohen's d = −0.54) and cadence  were significantly slower for those with leg spasticity compared to those without leg spasticity. The differences approached significance for single leg support , double leg support , and step time  but not base of support . There were small-to-moderate, statistically significant associations between overall spasticity scores and walking velocity  and single  and double support ; the associations were small and not statistically significant with cadence , base of support , and step time .Velocity  and energetics  resulting in changes in perceived (MSWS-12) and actual walking impairment in daily life. We further report on the severity of spasticity and its association with markers of walking dysfunction. Collectively, the breadth of possible alterations in ambulation, particularly the novel associations with spatial and temporal parameters of gait and community ambulation, underscores the importance of designing therapeutic strategies for optimizing spasticity and testing the effect for improving mobility in MS. Such interventions might target spasticity of the legs for improving spatial and temporal parameters of gait with downstream effects on performance and self-reported, physiological, and free-living measures of ambulation.The results of this study both replicate and extend previous research on spasticity and mobility outcomes in MS. For example, previous studies have reported that the presence of leg spasticity is associated with 6 MW, T25FW, and TUG performance, MSWS-12 scores, and O with MS , 17; we readmill  and we nOverall, we report that leg spasticity was present in more than half of the persons with MS and was associated with impairments in ambulation, including alterations in spatial and temporal parameters and free-living walking. This pervasive association between spasticity of the leg and ambulation, from the gait cycle through community walking, further highlights the importance of designing and testing interventional therapeutics for spasticity management and possible consequences for mobility in MS.


Adjuvant radiotherapy (RT) for left-sided breast cancer increases cardiac morbidity and mortality. For the heart, no safe radiation threshold has been established. Troponin T is a sensitive marker of myocardial damage. Our aim was to evaluate the effect of left-sided breast cancer RT on serum high sensitivity troponin T (hscTnT) levels and its association with cardiac radiation doses and echocardiographic parameters.A total of 58 patients with an early stage, left-sided breast cancer or ductal carcinoma in situ (DCIS) who received adjuvant breast RT without prior chemotherapy were included in this prospective, non-randomized study. Serum samples were taken before, during and after RT. An increase of hscTnT >30 % was predefined as significant. A comprehensive 2D echocardiograph and electrocardiogram (ECG) were performed before and after RT. Dose-volume histograms (DVHs) were generated for different cardiac structures.N = 12) had significantly higher radiation doses for the whole heart (p = 0.02) and left ventricle (p = 0.03) than patients without hscTnT increase . For the left anterior descending artery (LAD), differences between groups A and B were found in volumes receiving 15 Gy (p = 0.03) and 20 Gy (p = 0.03) Furthermore, after RT, the interventricular septum thickened (p = 0.01), and the deceleration time was prolonged (p = 0.008) more in group A than in group B.The hscTnT increased during RT from baseline in 12/58 patients (21 %). Patients with increased hscTnT values (group A, The increase in hscTnT level during adjuvant RT was positively associated with the cardiac radiation doses for the whole heart and LV in chemotherapy-naive breast cancer patients. Whether these acute subclinical changes increase the risk of excessive long-term cardiovascular morbidity or mortality, will be addressed in the follow-up of our patients. Postoperative radiotherapy (RT) for breast cancer is an essential part of adjuvant cancer treatment. RT reduces the risk of local recurrence by 50 % and the risk of breast cancer mortality by 16 % . In a reRadiation induced cardiac changes have been demonstrated with echocardiographic strain rate imaging , myocardIn this study, we included only chemotherapy-naive breast cancer patients to exclude chemotherapy-induced prior cardiotoxicity. The patients were studied prospectively using a cardiac biomarkers, comprehensive 2D echocardiography and 12-lead electrocardiogram (ECG) before and after adjuvant RT to detect subclinical cardiac changes. Furthermore, dose volume histograms (DVHs) for different cardiac structures were generated and correlated with serum markers and echocardiographic measurements.n = 59) or mastectomy (n = 1) without axillary or supraclavicular lymph node RT. Two patients were excluded from final analysis due to missing serum samples. Patients with prior adjuvant chemotherapy were excluded. Other exclusion criteria were age over 80 years, dialysis, recent acute myocardial infarction, symptomatic heart failure, chronic atrial fibrillation, pacemaker therapy and severe lung disease. The local ethical committee approved the protocol and all participants signed informed consent before study enrollment. The study was conducted from June 2011 to May 2013.This single centre, prospective, observational clinical study included 60 eligible female patients with early stage left-sided breast cancer or DCIS. All patients were treated with adjuvant conformal 3D RT after breast conserving surgery (All patients had 3D computer tomography (CT) treatment planning with Philips Big Bore CT  or Toshiba Aquilion LB  on a breast board in the supine position with their arms above their heads. CT slices (3 mm thickness) were used without intravenous contrast. Scanning was performed during free breathing in 56 patients, whereas 2 patients were scanned and treated using the voluntary deep inspiration breath hold (vDIBH) technique, which was implemented in our unit in April 2013 as part of clinical practice. In vDIBH, the breathing cycle was monitored with Varian real time position management (RPM) system . Treatment contouring and planning were done with Eclipse v.10 system . Planning target volume (PTV) covered the remaining breast tissue in 57 patients and the chest wall in one patient (mastectomy) with sufficient margins to account for the inter- and intrafraction movements (5–8 mm in our unit).Treatment doses were either 50 Gray (Gy) in 2 Gy fractions with or without additional boost  to tumor bed or 42.56 Gy in 2.66 Gy fractions (hypofractionation) over 3.5 weeks. Tangential photon fields were used in 57 patients and chest wall in one patient with mastectomy was treated with electron beams. Doses were calculated with anisotropic analytical algorithm  for photons and Electron Monte Carlo algorithm  for electrons. Dose volume histograms (DVH) of different structures were generated for each patient. To account for the different dosing schedules, an α/β-ratio of 3 was used for heart and lung to calculate 2 Gy equivalent doses.The heart, LV and LAD were contoured from the treatment planning CT scans as suggested by Feng et al. . All carHigh sensitivity cardiac troponin T  and B-type natriuretic peptide  were analyzed from serum samples taken before, after two (hypofractionated RT) or three  weeks of treatment and at the last day of RT. As the lowest detection limit of hscTnT was 5 ng/l, the values below this (<5 ng/l) were estimated to be 4 (lowest detection limit (LOD)/√2) when calculating the percentage increase from the baseline value . A predeTotal cholesterol levels (mmol/l) were measured at baseline under fasting conditions.A comprehensive echocardiography study and 12-lead ECG were performed at the baseline and at the completion of RT. All echocardiography examinations were performed using the same ultrasound machine  and a 1–5 MHz matrix-array X5-1 transducer by the same cardiologist certified by European Association of Echocardiography for adult transthoracic echocardiography. All images were acquired at rest. Subcostal imaging was performed in the supine position, while other imaging was performed with the patient in the lateral decubitus position with simultaneous superimposed ECG. Doppler recordings were acquired at the end of expiration during shallow breathing. Images were stored digitally for use with offline analysis software . Echocardiographic measurements were performed in a standardized manner according to the European guidelines .t-test for independent samples or the Mann–Whitney U test. Friedman’s analysis of variance was used for repeated measures of non-normal variables and the Wilcoxon signed ranks test was used to compare the hscTnT before RT vs. hscTnT after RT. Categorical data are expressed as numbers (%) of subjects. The Chi-squared test was used for categorical variables and the Fisher’s exact test was used when appropriate. The related samples Cochran’s Q test was used to study the change in dichotomous variables measures more than twice. Area under curve (AUC) was calculated using the trapezium rule in order to summarize the information from DVH. All the tests were two-sided and a p value <0.05 was considered statistically significant. Analysis was performed using IBM SPSS Statistics for Windows .Data are expressed as means ± standard deviation (SD) for normally distributed continuous variables and as medians with inter quartile range (IQR) for variables with non-normal distributions. The study groups were compared using the p = 0.31) and less thyroid hormone supplementation (p = 0.19).Baseline characteristics of the patients are presented in Table In the whole study population, hscTnT was detectable (≥5 ng/l) in 25 (43 %) patients before RT, in 28 (48 %) at 3 weeks and in 30 (52 %) patients after RT. The serum samples after RT were taken at the last day of RT .p = 0.08). However, hscTnT increased over 30 % from the baseline value in 12/58 (21 %) patients constituting the group A. In these 12 patients, hscTnT was detectable in 3 (25 %) before RT, in 9 (75 %) at 2–3 weeks and in 12 (100 %) patients after RT. The median (IQR) values at these time points were 4 (4–4.5)ng/l, 5.5 (4.5-6)ng/l and 7 (7–9.5)ng/l, respectively  hscTnT was detectable in 22 (48 %) at the beginning, 19 (41 %) at 2–3 weeks and 18 (39 %) after RT with median (IQR) values of 4(4–7), 4(4–6) and 4(4–6) ng/l, respectively.Median (IQR) hscTnT for the whole study population was 4 (4–6) ng/l before RT, 4 (4–6) ng/l at 3 weeks and 5 (4–7) ng/l after RT. The difference in hscTnT level before RT and after RT was not significant for the whole population (p = 0.72). The BNP change between the first and the last time point was −5 (−26 to 5) mmol/l in the group A vs. 5 (−14 to 22) mmol/l in the group B (p = 0.33).In the whole study population BNP levels were 58 (37–124), 69 (42–135) and 74 (34–126) mmol/l before RT, at 2–3 weeks and after RT, respectively . In addition to AUC, some relevant dose-volume parameters  were separately tested  accompanied with a change in LV diastolic function as the deceleration time increased (p = 0.008) among group A more than in group B. In other LV diastolic parameters, the mitral E-peak decreased in both groups. The decrease in the LV end diastolic and end systolic diameters in the group A were not statistically significant compared with group B .In group A, the increase in hscTnT was accompanied by minor changes in the echocardiographic measurements as presented in Table p = 0.82).Normal sinus rhythms were present in all ECG recordings with no signs of atrial or ventricular abnormalities. RT caused moderate T-wave alterations in 3/12 (25 %) recordings among group A and 13/46 (28 %) among group B  . In our Increasing doses to LV correlate with myocardial perfusion defects , 7, 32. The LAD runs in the sulcus between the left and right ventricle. Its anatomical location in relation to chest wall varies from one patient to another. The LAD is, however, generally at the most anterior part of the LV and therefore, the radiation doses to LAD in left sided breast cancer RT can be substantial. In coronary vessels, the acute RT induced damage may later manifest as thickening and fibrosis of the vessel walls and increased local atherosclerosis. The coronary arteries should be considered as a serial-type organ, where the damage to one small part affects the function of whole the unit. In our patients, the DVHs of the LAD differ clearly after 5 Gy and converge only at high doses. The AUC analysis of the LAD did not reach statistical significance due to variation of doses and the limited number of patients.LV’s ejection fraction (LVEF), a widely used marker of the LV’s systolic function in oncology, did not decrease in our patients after RT. This finding is similar than with Lo Q et al. , who detDiastolic changes in LV’s function were observed in both groups such as lower mitral E peak. As RT induces inflammation and later fibrinogenesis in tissues , it is lHypertension is a known additive risk factor for RT induced cardiotoxicity . In our HscTnT is a sensitive marker of acute myocardial damage. In general, greater damage causes a greater troponin release and indicates worse prognosis. In this study, the increases in hscTnT values associated with increased cardiac radiation doses for the whole heart and LV. In daily RT treatment planning, at least the whole heart should be contoured as an organ at risk for left sided breast cancer RT in order to keep the cardiac dose as low as possible. Evolving radiation techniques will help to accomplish the cardiac dose sparing. Patient derived risk factors, such as hypertension, are still important and need special caution and guidance. Echocardiography can measure RT induced subclinical cardiac changes immediately after breast cancer RT and should be used in the later follow up of patients. Likewise, an expert consensus from 2013 recommends routine echocardiography after left sided breast cancer RT for all breast cancer survivors in 5–10 years to screen for radiation induced heart disease .The elevation on hscTnT levels suggests that adjuvant RT causes subclinical myocardial damage in patients with left-sided breast cancer. As the increase in hscTnT associates with increased cardiac radiation doses all efforts should be made to keep the radiation to the heart as low as possible. Whether these acute subclinical changes in echocardiography increase the risk of excessive long-term cardiovascular morbidity or mortality in our patients will be addressed in the later follow-up.


Quantification of the longitudinal- and transverse relaxation time in the myocardium has shown to provide important information in cardiac diagnostics. Several methods are currently available for cardiac relaxation time mapping but they generally demand a long breath hold to measure either T1 or T2 in a single 2D slice. In order to make quantification of relaxation parameters in the myocardium clinically applicable, the methods must be improved in speed and coverage. In this work we propose a novel method for 3D interleaved T1 and T2 quantification of the whole left ventricular myocardium within one single breath hold.The sequence is based on a 3D spoiled Turbo Field Echo sequence using inversion recovery with interleaved T2 preparation and is referred to as 3D-QALAS (3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse). Quantification of both T1 and T2 in a volume of 13 slices with a resolution of 2.0 × 2.0 × 6.0 mm is obtained. The acquisition time is restricted to 230 ms during end diastole to avoid artifacts from cardiac motion. Data acquisition is performed once after a T2 preparation pulse and four times after a T1 sensitizing inversion pulse (5 heartbeats). This acquisition scheme is repeated three times to sample the 3D k-space, resulting in a breath hold of 15 heartbeats. The sequence was validated in both phantoms and healthy volunteers using a Philips Ingenia 3T scanner. The effect of different heart rates, flip angles and deliberately applied arrhythmias were simulated and investigated in phantoms.Relaxation times in phantoms correlate well with reference methods, Inversion Recovery for T1 and Multi Echo for T2. Quantification of T1 and T2 using 3D QALAS showed no dependence on heart rate, flip angle or arrhythmia within the clinically relevant range. In vitro T1 measurements with 3D QALAS for different heart rates, which has shown to be challenging for other methods, are shown in Figure 3D QALAS allows quantification of both T1 and T2 in the whole left ventricular myocardium within one breath hold, making T1 and T2 quantification clinically applicable to a broader spectrum of diseases.Swedish Research Council and Swedish Heart-Lung Foundation.


Myocardial longitudinal relaxation time  is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T1 values in acute STEMI patients is unknown. We aimed to assess the clinical significance of infarct tissue characteristics using native T1 cardiac magnetic resonance (CMR).We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. Native T1 CMR  3 (3) 5) was measured in myocardial regions-of-interest. The area-at-risk and infarct territory were depicted with T1 mapping and late gadolinium contrast enhancement imaging, respectively. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up.300 STEMI patients  gave informed consent and had CMR (14 July 2011 - 22 November 2012). Of these, 288 STEMI patients had evaluable T1 maps and follow-up assessments (median duration 845 days). Infarct size was 18 ±14% of left ventricular mass. Microvascular obstruction occurred in 160 (55.6%) patients. Native T1 within the area-at-risk (1097 ±52 ms) was higher than in the remote zone  or infarct core (996.9 (57.3); p<0.01). In multivariable linear regression, native T1 in the area-at-risk was independently and negatively associated with age, initial systolic blood pressure and TIMI coronary flow grade at presentation , independent of LVEF, left ventricular end-diastolic volume (LVEDV) or infarct size. Similar findings were observed for T1 core values, which were also independently associated with Killip class.At 6 months, LVEDV change was available for 262 patients and was increased by ≥20% in 30 (11.5%) patients of whom 23 (76.7%) had microvascular obstruction at baseline. T1 in the infarct core was a multivariable predictor of adverse remodeling ; p=0.048).288 (100%) patients had longer term follow-up completed. The median duration of follow-up was 845 days. Thirty (10.4%) patients died or experienced a heart failure event and 13 (4.5%) of these patients died or experienced a heart failure hospitalization post-discharge. Native T1 in the area-at-risk was a predictor of all-cause death or heart failure post-discharge  including after adjustment for LVEF at baseline (p=0.018) and LVEDV at baseline (p=0.013).In acute STEMI patients, infarct zone tissue characteristics predict left ventricular remodeling and long-term health outcomes, independent of infarct size and LV function.N/A.