The Relative Apical Sparing Strain Pattern in Severe Aortic Valve Stenosis: A Marker of Adverse Cardiac Remodeling.

BACKGROUND: The presence of a relative apical sparing (RAS) echocardiographic strain pattern raises a suspicion of underlying cardiac amyloidosis (CA). However, it is also increasingly observed in patients with aortic stenosis (AS). We aimed to evaluate the prevalence, dynamics, and clinical characteristics of the RAS strain pattern in severe AS patients who had been referred for surgical aortic valve replacement (SAVR). METHODS: A total of 77 patients with severe AS and without CA were included with a mean age of 70 (62-73) years, 58% female, a mean aortic valve area index of 0.45 ± 0.1 cm2/m2, and a mean gradient of 54.9 (45-70) mmHg. RESULTS: An RAS strain pattern was detected in 14 (18%) patients. RAS-positive patients had a significantly higher LV mass index (125 ± 28 g/m2 vs. 91 ± 32, p = 0.001), a lower LV ejection fraction (62 ± 12 vs. 68 ± 13, p = 0.040), and lower global longitudinal strain (-14.9 ± 3 vs. -18.7 ± 5%, p = 0.002). RAS strain pattern-positive patients also had higher B-type natriuretic peptide (409 (161-961) vs. 119 (66-245) pg/L, p = 0.032) and high-sensitivity troponin I (15 (13-29) vs. 9 (5-18) pg/L, p = 0.026) levels. Detection of an RAS strain pattern was strongly associated with increased LV mass index (OR 1.03, 95% CI 1.01-1.06, p < 0.001). The RAS strain pattern had resolved in all patients by 3 months after SAVR. CONCLUSIONS: Our findings suggest that the RAS strain pattern can be present in patients with severe AS without evidence of CA. The presence of an RAS strain pattern is associated with adverse LV remodeling, and it resolves after SAVR.

Electrocardiographic Markers of Adverse Left Ventricular Remodeling and Myocardial Fibrosis in Severe Aortic Stenosis.

The optimal timing for aortic valve replacement (AVR) in aortic stenosis (AS) is still controversial and may be guided by markers of adverse left ventricular (LV) remodeling. We aim to assess electrocardiographic (ECG) strain in relation to LV remodeling and myocardial fibrosis. 83 severe AS patients underwent surgical AVR, with preoperative 12-lead ECG, cardiovascular magnetic resonance with T1 mapping and echocardiography with global longitudinal strain analysis. Collagen volume fraction (CVF) was measured in myocardial biopsies sampled during AVR. Patients with ECG strain had more severe AS, more advanced LV remodeling and evidence of heart failure. Patients with ECG strain had more diffuse fibrosis, as evident by higher mean native T1 values (974.8 ± 34 ms vs. 946.5 ± 28 ms, p < 0.001). ECG strain was the only predictor of increased LV mass index on multivariate regression analysis (OR = 7.10, 95% CI 1.46-34.48, p = 0.02). Patients with persistent ECG strain at 1 year following AVR had more advanced LV remodeling and more histological fibrosis (CVF 12.5% vs. 7.3%, p = 0.009) at baseline assessment. Therefore, ECG strain is a marker of adverse LV remodeling and interstitial myocardial fibrosis. Lack of improvement in ECG strain following AVR indicates more advanced baseline LV injury and higher levels of myocardial fibrosis.

Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study.

Myocardial fibrosis in aortic stenosis is associated with worse survival following aortic valve replacement. We assessed myocardial fibrosis in severe AS patients, integrating echocardiographic, cardiovascular magnetic resonance (CMR) and histological data. A total of 83 severe AS patients (age 66.4 ± 8.3, 42% male) who were scheduled for surgical AVR underwent CMR with late gadolinium enhancement and T1 mapping and global longitudinal strain analysis. Collagen volume fraction was measured in myocardial biopsies (71) that were sampled at the time of AVR. Results. CVF correlated with imaging and serum biomarkers of LV systolic dysfunction and left side chamber enlargement and was higher in the sub-endocardium compared with midmyocardium (p<0.001). CVF median values were higher in LGE-positive versus LGE-negative patients [28.7% (19-33) vs 20.7% (15-30), respectively, p=0.040]. GLS was associated with invasively (CVF; r=-0.303, p=0.013) and non-invasively (native T1; r=-0.321, p<0.05) measured myocardial fibrosis. GLS and native T1 correlated with parameters of adverse LV remodelling, systolic and diastolic dysfunction and serum biomarkers of heart failure and myocardial injury. Conclusion. Our data highlight the role of myocardial fibrosis in adverse cardiac remodelling in AS. GLS has potential as a surrogate marker of myocardial fibrosis, and high native T1 and low GLS values differentiated patients with more advanced cardiac remodelling.

Prognostic value of myocardial fibrosis in severe aortic stenosis: study protocol for a prospective observational multi-center study (FIB-AS).

BACKGROUND: Adverse cardiac remodeling with a myocardial fibrosis as a key pathophysiologic component may be associated to worse survival in aortic stenosis (AS) patients. Therefore, with the application of advanced cardiac imaging we aim to investigate left ventricular myocardial fibrosis in severe AS patients undergoing aortic valve replacement (AVR) and determine its impact with post-intervention clinical outcomes. METHODS: In a prospective, observational, cohort study patients with severe AS scheduled either for surgical or transcatheter AVR will be recruited from two tertiary heart centers in Denmark and Lithuania. All patients will receive standard of care in accordance with the current guidelines and will undergo additional imaging testing before and after AVR: echocardiography with deformation analysis and cardiovascular magnetic resonance (CMR) with T1 parametric mapping. Those undergoing surgical AVR will also have a myocardial biopsy sampled at the time of a surgery for histological validation. Patients will be recruited over a 2-year period and followed up to 2 years to ascertain clinical outcomes. Follow-up CMR will be performed 12 months following AVR, and echocardiography with deformation analysis will be performed 3, 12, and 24 months following AVR. The study primary outcome is a composite of all-cause mortality and major adverse cardiovascular events. DISCUSSION: Despite continuous effort of research community there is still a lack of early predictors of left ventricular decompensation in AS, which could improve patient risk stratification and guide the optimal timing for aortic valve intervention, before irreversible left ventricular damage occurs. Advanced cardiac imaging and CMR derived markers of diffuse myocardial fibrosis could be utilized for this purpose. FIB-AS study is intended to invasively and non-invasively assess diffuse myocardial fibrosis in AS patients and investigate its prognostic significance in post-interventional outcomes. The results of the study will expand the current knowledge of cardiac remodeling in AS and will bring additional data on myocardial fibrosis and its clinical implications following AVR. ETHICS/DISSEMINATION: The study has full ethical approval and is actively recruiting patients. The results will be disseminated through scientific journals and conference presentations. TRIAL REGISTRATION: ClinicalTrials.govNCT03585933. Registered on 02 July 2018.

Correction to: Prevalence and prognostic value of late gadolinium enhancement on CMR in aortic stenosis: meta-analysis.

The original version of this article, published on 12 August 2019, unfortunately contained a mistake. The funding note was incorrect; the correct funding note is given below.

Prevalence and prognostic value of late gadolinium enhancement on CMR in aortic stenosis: meta-analysis.

OBJECTIVES: The aim of this study was to investigate the prevalence and prognostic value of late gadolinium enhancement (LGE), as assessed by cardiovascular magnetic resonance (CMR) imaging, in patients with aortic stenosis. METHODS AND RESULTS: A systematic search of PubMed and EMBASE was performed, and observational cohort studies that analysed the prevalence of LGE and its relation to clinical outcomes in patients with aortic stenosis were included. Odds ratios were used to measure an effect of the presence of LGE on both all-cause and cardiovascular mortality. Nineteen studies were retrieved, accounting for 2032 patients (mean age 69.8 years, mean follow-up 2.8 years). We found that LGE is highly prevalent in aortic stenosis, affecting half of all patients (49.6%), with a non-infarct pattern being the most frequent type (63.6%). The estimated extent of focal fibrosis, expressed in % of LV mass, was equal to 3.83 (95% CI [2.14, 5.52], p < 0.0001). The meta-analysis showed that the presence of LGE was associated with increased all-cause (pooled OR [95% CI] = 3.26 [1.72, 6.18], p = 0.0003) and cardiovascular mortality (pooled OR [95% CI] = 2.89 [1.90, 4.38], p < 0.0001). CONCLUSIONS: LGE by CMR is highly prevalent in aortic stenosis patients and exhibits a substantial value in all-cause and cardiovascular mortality prediction. These results suggest a potential role of LGE in aortic stenosis patient risk stratification. KEY POINTS: • Up to the half of aortic stenosis patients are affected by myocardial focal fibrosis. • Sixty-four percent of focal fibrosis detected by LGE-CMR is non-infarct type. • The presence of focal fibrosis triples all-cause and cardiovascular mortality.

Transthyretin cardiac amyloidosis in aortic stenosis: Prevalence, diagnostic challenges, and clinical implications.

Transthyretin cardiac amyloidosis (ATTR-CA) is a challenging and underdiagnosed cause of heart failure. Advances in cardiac imaging have enabled noninvasive diagnosis of ATTR-CA, causing the recent upsurge in disease awareness and detection. ATTR-CA has been increasingly recognized in patients with degenerative aortic stenosis (AS). With the growing number of elderly patients undergoing aortic valve intervention, the identification of ATTR-CA in this group of patients is of high clinical importance. Timely and correct diagnosis is essential for amyloid-directed therapies, as well as deciding on the AS treatment strategy. This review provides a comprehensive overview of the recent studies investigating coexistence of these two entities. We present the data on the prevalence of ATTR-CA in AS and their prognostic associations. As the diagnosis of ATTR-CA may be challenging, special attention is paid to the diagnostic utility of different imaging modalities, namely, echocardiography, cardiovascular magnetic resonance, nuclear imaging, and distinctive imaging features, in patients with dual pathology. We also present a flowchart summarizing integrated imaging in patients with suspected ATTR-CA.

Predictors of ischaemic mitral regurgitation recurrence in patients undergoing combined surgery: additional value of cardiovascular magnetic resonance imaging.

OBJECTIVES: We aimed to evaluate (i) the effectiveness of combined surgery (coronary artery bypass grafting with restrictive mitral valve annuloplasty) and (ii) the late gadolinium enhancement cardiovascular magnetic resonance-based predictors of ischaemic mitral regurgitation (IMR) recurrence. METHODS: The prospective analysis included 40 patients with multivessel coronary artery disease, IMR >II° and left ventricular (LV) dysfunction undergoing combined surgery. The degree of IMR and LV parameters were assessed preoperatively by transthoracic echocardiography, 3D transoesophageal echocardiography and cardiovascular magnetic resonance and postoperatively by transthoracic echocardiography. The effective mitral valve repair group (n = 30) was defined as having recurrent ischaemic mitral regurgitation (RIMR) ≤II° at the end of follow-up (25 ± 11 months). RESULTS: The surgery was effective: freedom from RIMR >II° at 1 and 2 years after surgery was 80% and 75%, respectively. Using multivariable logistic regression, 2 independent predictors of RIMR >II° were identified: ≥3 non-viable LV segments (odds ratio 22, P = 0.027) and ≥1 non-viable segment in the LV posterior wall (odds ratio 11, P = 0.026). Using classification trees, the best combinations of cardiovascular magnetic resonance-based and 3D transoesophageal echocardiography-based predictors for RIMR >II° were (i) posterior mitral valve leaflet angle >40° and LV end-systolic volume index >45 ml/m2 (sensitivity 100%, specificity 89%) and (ii) scar transmurality >68% in the inferior LV wall and EuroSCORE II >8 (sensitivity 83%, specificity 78%). CONCLUSIONS: There is a clear relationship between the amount of non-viable LV segments, especially in the LV posterior and inferior walls, and the recurrence of IMR after the combined surgery.

Prevalence and clinical significance of extracardiac findings in cardiovascular magnetic resonance.

OBJECTIVE: In cardiac magnetic resonance imaging (CMR), incidental pathological findings are frequently found outside the investigated cardiovascular system. Some of these findings might have clinical implications. The aim of this study was to determine the prevalence of incidental extracardiac findings (ECF) in CMR and their clinical significance. METHODS: A total of 4165 CMR reports from 2009-2012 were retrospectively reviewed for ECF. Two hundred-twenty reports with ECF were found. For each case, we obtained information on sex, age of the patient, reported ECF and radiologist recommendation. Follow-up data were analyzed by reviewing available electronic medical records. ECF was considered clinically significant if there was an associated diagnosis, additional treatment or further investigations in the clinical follow-up data. RESULTS: In total, 356 ECF were recorded in 220 (5.3%) CMR reports. Sixty (23.7%) of the 253 ECF with follow-up data available were clinically significant. The most prevalent ECF were pleural effusions (n=54), kidney cysts (n=54), diffuse lung parenchyma changes (n=33) and liver cysts (n=29). Adrenal pathology (n=3, 100% significant), renal masses (n=3, 100%) and pulmonary masses (n=5, 62.5%) were the most clinically significant ECF. Although prevalence of these ECF was low, they were significant particularly frequently. When radiologist recommendations for further investigation were present in the report, the frequency of clinically significant ECF was higher compared to reports with no further investigation recommended (p<0.001). CONCLUSION: In this study, ECF in CMR were reported not very commonly (5.3%). A substantial part of ECF was clinically significant, changing patient diagnosis or management, with an overall prevalence of 1.3%.

Could careful patient selection for renal denervation warrant a positive effect on arterial stiffness and left ventricular mass reduction?

AIMS: After the sequence of Symplicity HTN trials, the impact of the procedure on lowering blood pressure (BP) and cardiovascular risk is still debatable. We present initial results of the multimodal pilot study that aimed at carefully selecting proper patients and investigating the effects of RASD on cardiac morphology and central haemodynamic parameters in 15 patients with resistant arterial hypertension prior and 6 months after RASD. METHODS AND RESULTS: The multimodal (applanation tonometry, echocardiography and cardiac magnetic resonance (CMR)) study findings have shown a significant BP decrease (190/112 ± 23/12 to 153/91 ± 18/11 mm Hg, P < 0.002), a decrease of the arterial markers (carotid-femoral pulse wave velocity decreased from 11.46 ± 2.92 m/s to 9.17 ± 2.28 m/s and the augmentation index decreased from 25.47 ± 10.55 to 21 ± 12.19, P < 0.006), a significant left ventricular mass index decrease by 10% both by echocardiography (140.83 ± 38.46 to 115.26 ± 25.37 g/m2, n = 14, P < 0.001) and CMR (108.32 ± 39.02 to 97.25 ± 30.06 g/m2, n = 15, P = 0.003). A significant decrease of CMR retrograde flow volume in the ascending aorta non-dependent on BP was also found. CONCLUSIONS: Our study is characterised by strict and extensive patient selection criteria for renal artery sympathetic denervation (RASD), which seem to warrant a positive effect of the procedure on BP, arterial stiffness and left ventricular mass 6 months after RASD, although it should be confirmed in larger controlled trials.

Prediction of long-term segmental and global functional recovery of hibernating myocardium after revascularisation based on low dose dobutamine and late gadolinium enhancement cardiovascular magnetic resonance.

BACKGROUND: This study sought to evaluate the relation between long-term segmental and global functional outcome after revascularisation in patients with chronic ischaemic left ventricular dysfunction (LVD) and baseline markers of viability: late gadolinium enhancement (LGE) transmurality and contractile reserve (CR). METHODS: Forty-two patients with chronic ischaemic LVD underwent low-dose dobutamine- (LDD) and late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) before surgical or percutaneous revascularisation. Regional and global left ventricular (LV) functions and LGE were repeatedly assessed 6 ± 1 and 35 ± 6 months after revascularisation. In total, 319 at baseline dysfunctional and successfully revascularised segments were available for statistical analysis. RESULTS: The likelihood of long-term functional improvement was directly related to the presence of CR and inversely related to both the LGE and the degree of contractile dysfunction at baseline. The time course of functional improvement was protracted, with significantly more delay in segments with more extensive LGE (p = 0.005) and more severe contractile dysfunction at baseline (p = 0.002). The presence of CR was the predictor of earlier functional improvement (p < 0.0001). Using a definition of viable segment as a segment without any LGE or with any LGE and producing CR during LDD stimulation, ≥ 55% of viable segments from all dysfunctional and revascularised segments in a patient was the only independent predictor of significant improvement (≥ 5%) in the left ventricular ejection fraction (LVEF) after revascularisation, with a 72% sensitivity and an 80% specificity (AUC 0.76, p = 0.014). Reverse LV remodelling was observed in patients who had a significant amount of viable myocardium successfully revascularised. CONCLUSIONS: In patients with chronic ischaemic LVD, improvement of dysfunctional but viable myocardium can be considerably delayed. Both the likelihood and the time course of functional improvement are related to the LGE, CR and the degree of contractile dysfunction at baseline. At 35 ± 6 months after revascularisation, patients with ≥55% of viable segments from all dysfunctional and revascularised segments significantly improve LVEF and experience reverse LV remodelling. A combination of LDD-CMR and LGE-CMR is a simple and powerful tool for identifying which patients with impaired LV function will benefit from revascularisation.

An assessment of iron overload in children treated for cancer and nonmalignant hematologic disorders.

UNLABELLED: Our goal was to assess the natural fate of iron overload (IO) following transfusions of packed red blood cells (PRBCs) in children treated for cancer and nonmalignant disorders according to the intensity level of their treatment. Sixty-six children were followed up from February 2010 to March 2013. The transfusion burden was compared between three treatment intensity groups assigned according to the Intensity of Treatment Rating Scale 3.0 (ITR-3). IO was assessed by serial measurements of serum ferritin (SF) (n= 66) and quantification of tissue iron by magnetic resonance imaging (MRI) (n=12). Of the children studied, 36 % (24/66) received moderately intensive treatment (level 2), 21 % (14/ 66) received very intensive treatment (level 3), and 42 % (28/ 66) received the most intensive treatment (level 4). The number of PRBC (p=0.016), the total transfused volume (p= 0.026), and transfused volume adjusted to body weight (p= 0.004) were significantly higher in the level 4 group. By the median follow-up time of 35.5 months (range 8­133), 21­ 29 % of patients (including level 2 and level 3 children) had SF >1,000 µg/l 1 year after cessation of transfusions. The slowest decrease of SF was observed in the level 4 group. Initial MRI examination demonstrated either mild or moderate IO in the liver and spleen. Repetitive MRI showed significant improvement in relaxation time between the initial and follow-up MRI performances in the liver (5.9 vs. 8.6 ms, p= 0.03) and the spleen (4.3 vs. 8.8 ms, p=0.03). CONCLUSION: IO diminished over time, but in the level 4 patients, it was detectable for years after cessation of transfusions.

Complicated congenital gluteal arteriovenous malformation with hemorrhage in pregnancy.

Extracranial congenital arteriovenous malformations (AVMs) are rare clinical entities that can be progressive in nature. The influence of pregnancy on lesion progression has been discussed in the past. This report presents an unusual case of 23-year-old primigravida woman who presented at 36 weeks' gestation with complicated necrotic ulceration and hemorrhage of the right gluteal region. A hyperpigmented mark with varicosities was initially noted at birth, but during pregnancy it showed remarkable progression and was first identified as an AVM. After hemorrhage control and induced delivery, the lesion was successfully treated with several embolizations. Complete wound healing was achieved, but because of partial recurrence at 3 years, repeat embolization was performed, with satisfactory clinical improvement and residual 25% arteriovenous shunting on transarterial lung perfusion scintigraphy study. AVM complications during pregnancy are uncommon, and this case supports the prior opinion that pregnancy can stimulate lesion progression. Especially in undiagnosed and previously untreated cases, this can lead to life-threatening complications for the mother and fetus. Long-term lesion management usually requires combined endovascular and surgical treatment.

Isolated nasal amyloidosis: a case report.

Amyloidosis is a rare condition characterized by the deposition of abnormal protein filaments into the extracellular tissue. Only 16 cases of true primary idiopathic amyloidosis localized in the nose and the paranasal sinuses have previously been reported. We present a case of localized amyloidosis involving the sinonasal cavities and the nose in a 53-year-old woman. Our patient was operated on as a typical case of chronic rhinosinusitis with polyps, but after 2 years, the patient came back with severe symptoms of nasal obstruction and pain in the frontal and maxillary regions with proptosis of both eyes. Magnetic resonance imaging revealed sinonasal-intraorbital masses. Primary amyloidosis (AL type) was confirmed by tissue biopsy. A systemic workup for additional amyloid deposits revealed no evidence of other diseases. Extended surgery produced a symptomatic improvement.

Age-dependent heterogeneity of familiar hypertrophic cardiomyopathy phenotype: a role of cardiovascular magnetic resonance.

In this case report, we present familiar hypertrophic cardiomyopathy with age-dependent heterogeneity of the disease phenotype among the members of one family who carry the same mutation of the myosin-binding protein C gene. Phenotypic heterogeneity is common in patients with familial forms of hypertrophic cardiomyopathy, both in clinical expression and outcome. Compared with other noninvasive cardiac imaging modalities, cardiovascular magnetic resonance provides an opportunity to more accurately characterize the varying phenotypic presentations of hypertrophic cardiomyopathy.