The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease.

Introduction: We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF. Methods: We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy. Results: We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement. Conclusion: 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients.

Feasibility and safety of left bundle branch area pacing in cardiac amyloidosis. A single center experience.

BACKGROUND: Conventional right ventricle (RV) pacemaker stimulation has been associated with worse clinical outcomes in patients with cardiac amyloidosis (CA). Left bundle branch area pacing (LABPP) has been suggested as a promising alternative. We sought to assess the safety, feasibility, and outcomes of LABPP in patients with CA. METHODS: We retrospectively analyzed echocardiography and pacing parameters and clinical outcomes in 23 consecutive patients with CA and LBBAP implanted from June 2020 to October 2022. RESULTS: LBBAP was successfully performed in 22 over 23 patients (19 male, 78.6 ± 11.7 years, 20 ATTR, mean LVEF 45.5 ± 16.2%). After the procedure, 9 patients showed Qr pattern and 11 a qR pattern in V1 on ECG. Average procedure time was 67 ± 28 min. After 7.7 ± 5.2 months follow-up, no procedure-related complications had occurred. Although, a significant reduction in QRS width (p = .001) was achieved, we did not observe significant changes in LVEF and Nt ProBNP at 6 months of follow-up. Pacing parameters were stable during follow-up: LBB capture threshold and R wave amplitude were 1.0 ±  0.5 V and 10.6 ± 6.0 mV versus 0.8 ±  0.1 V, p = .21 and 10.6 ± 5.1 mV (p = .985) at follow up. CONCLUSION: LBBAP is safe and feasible pacing technique for patients with CA. LBBAP is associated with significant narrowing of QRSd without worsening in LVEF and Nt-proBNP.

Prognostic value of exercise echocardiography in patients with wild-type transthyretin amyloidosis.

Background: Wild-type transthyretin amyloidosis is a systemic disease with predominantly cardiac symptoms. The aim of this study was to assess the short-term prognosis of these patients through contractile reserve measured by stress echocardiography, given the usefulness that this parameter has demonstrated in other populations. We considered major events as death from any cause and hospitalization for heart failure. Material and methods: We conducted a study with a 1-year follow-up in 11 patients who were proposed to undergo a stress echocardiogram, with the follow-up as usual according to their doctor. We excluded pacemaker wearers, patients with permanent atrial fibrillation, those incapable of exertion at low loads, and those with poor acoustic windows. Results: We found that contractile reserve estimated by right ventricular free wall longitudinal strain is correlated with a lower rate of death (all of them cardiovascular deaths) and hospitalizations for heart failure. Conclusions: Contractile reserve assessed by right ventricular free wall longitudinal strain is a predictor of major events in patients with wild-type transthyretin cardiac amyloidosis.

Exploring the potential relationship between collagen cross-linking and impaired myocardial relaxation in Marfan syndrome: An observational study using serum biomarkers.

BACKGROUND: Increased collagen cross-linking (CCL) has been described in hypertensive cardiomyopathy by means of reduced serum ratio of serum carboxyterminal telopeptide of collagen type I (CITP) to matrix metalloproteinase-1 (MMP1). Previous studies have demonstrated the existence of primary impaired diastole in patients with Marfan syndrome (MFS), but little is known about the pathophysiology of this condition. METHODS: 60 MFS patients (without previous cardiovascular surgery or significant valvular regurgitation) and 24 healthy controls (age and sex-matched) were enrolled. All participants underwent a comprehensive transthoracic echocardiographic study, including left atrial and left ventricular speckle-tracking strain analysis. CITP and MMP1 were measured in peripheral blood. RESULTS: All participants had normal diastolic function according to guidelines. Peak left atrial strain in the reservoir phase (LASr) was significantly reduced in the MFS cohort compared to controls (32.2 ± 9.4 vs 43.9 ± 7.0%; p < 0.001). Serum CITP and CITP:MMP1 ratio were lower among MFS patients, showing significant correlations with LASr (R = 0.311; p = 0.020 and R = 0.437; p = 0.001, respectively). The MFS cohort was divided into quartiles of LASr. MFS patients in the lowest quartile of LASr (<26%) had significantly lower values of CITP:MMP1 ratio compared to the other quartiles. CONCLUSIONS: The analysis of serum biomarkers revealed the presence of increased CCL in association with reduced LASr in the MFS cohort. Our results suggest that excessive CCL may play a role in the development of primary myocardial impairment in these patients. Future studies are needed to confirm our findings and evaluate the prognostic role of CCL markers in the MFS population.

Left atrial strain in the assessment of diastolic function: providing new insights into primary myocardial dysfunction in Marfan syndrome.

Previous studies using conventional echocardiographic measurements have reported subclinical left ventricular (LV) diastolic abnormalities in patients with Marfan syndrome (MFS). Left atrial (LA) strain allows an accurate categorization of LV diastolic dysfunction. We aimed to characterize LV myocardial performance in a cohort of MFS patients using STE-derived measurements (LV and LA strain) along with conventional echocardiographic parameters. We studied 127 adult patients with MFS (no prior cardiac surgery or significant valvular regurgitation) and 38 healthy controls. We performed detailed echocardiograms and selected left atrial reservoir strain (LASr) as a surrogate of impaired relaxation. Additionally, we searched for possible determinants of LASr in patients with MFS, with a special focus on the elastic properties of the aorta. In spite of lower E-wave, septal and lateral e' velocities and average E/e' ratio in MFS patients, all participants had normal diastolic function according to current guidelines. MFS patients exhibited reduced LV global longitudinal strain (19.3 ± 2.6 vs 21.6 ± 2.1%, p < 0.001) and reduced LASr (32.9 ± 8.5 vs 43.3 ± 7.8%, p < 0.001) compared to controls. In the MFS cohort, we found weak significant (p < 0.05) correlations between LASr and certain parameters: E/A ratio (R = 0.258), E wave (R = 0.226), aortic distensibility (R = 0.222), stiffness index (R = - 0.216), LV ejection fraction (R = 0.214), lateral e' (R = 0.210), LV end-systolic volume index (R = - 0.210), LV global longitudinal strain (R = 0.201), septal e' (R = 0.185). After multivariate analysis, only LV end-systolic volume index and E/A ratio maintained a weak independent association with LASr (R = - 0.220; p = 0.017 and R = 0.199; p = 0.046, respectively). In conclusion, LASr is reduced in patients with MFS, which may represent an early stage of LV diastolic dysfunction. LASr is not determined by the elastic properties of the aorta, suggesting that impaired myocardial relaxation is a primary condition in MFS.

Right ventricular function and dyssynchrony in Brugada syndrome: Highlighting the importance of the mechanical substrate in the right ventricular outflow tract.

BACKGROUND: Current evidence suggests that Brugada syndrome (BrS), far from being a purely electrical condition, is associated with subtle mechanical abnormalities primarily affecting the right ventricle (RV). We aimed to characterize RV function in BrS and investigate the echocardiographic profile of patients with arrhythmic events, with a special focus on parameters of RV dyssynchrony using speckle-tracking echocardiography (STE). METHODS: An echocardiogram was performed in 71 BrS patients and 25 healthy controls. STE was performed to assess regional and global RV mechanics, including RV outflow tract shortening (RVOTS). RVOT contraction time was considered to calculate the modified RV mechanical dispersion (RVMDm). Arrhythmic events were prospectively evaluated in the BrS cohort. RESULTS: Compared to controls, BrS patients showed subtle contractile abnormalities, including impaired RV longitudinal strain, higher RV index of myocardial performance (RIMP) and lower RVOTS. BrS patients also exhibited a greater contraction delay between the lateral and the septal aspect of the RV. After a median follow-up of 7.3 year (IQR 5.2-10.8), 6 patients presented malignant arrhythmic events. RIMP >0.50, RVOTS <16.2% and RVMDm > 42 ms showed high sensitivity for the identification of BrS patients with arrhythmic events during follow-up. CONCLUSIONS: Subtle RV mechanical abnormalities were present in BrS patients. RIMP and RVOTS, a novel STE-derived parameter, were found to be sensitive markers of arrhythmic events. Adding the RVOT contraction time to the analysis of RVMD may help identify patients at higher risk, reflecting the importance of the RVOT mechanical substrate in the assessment of the arrhythmic risk in BrS.

Clinical profile and outcome of cardiac amyloidosis in a Spanish referral center.

INTRODUCTION AND OBJECTIVES: Cardiac amyloidosis (CA) is produced by amyloid fiber deposition in the myocardium. The most frequent forms are those caused by light chains (AL) and transthyretin (ATTR). Our objective was to describe the diagnosis, treatment and outcomes of CA in a specialized Spanish center. METHODS: We included all patients diagnosed with CA in Hospital Universitario Puerta de Hierro Majadahonda from May 2008 to September 2018. We analyzed their clinical characteristics, outcomes, and survival. RESULTS: We included 180 patients with CA, of whom 64 (36%) had AL (50% men; mean age, 65±11 years) and 116 had ATTR (72% men; mean age 79±11 years; 18 with hereditary ATTR). The most common presentation was heart failure in both groups (81% in AL and 45% in ATTR, P <.01). Other forms of presentation in ATTR patients were atrial arrhythmias (16%), conduction disorders (6%), and incidental finding (6%); 70 patients (40%), had a previous alternative cardiac diagnosis. Diagnosis was noninvasive in 75% of ATTR patients. Diagnostic delay was higher in ATTR (2.8±4.3 vs 0.6±0.7 years, P <.001), but mortality was greater in AL patients (48% vs 32%, P=.028). Independent predictors of mortality were AL subtype (HR, 6.16; 95%CI, 1.56-24.30; P=.01), female sex (HR, 2.35; 95%CI, 1.24-4.46; P=.01), and NYHA functional class III-IV (HR, 2.07; 95%CI, 1.11-3.89; P=.02). CONCLUSIONS: CA is a clinical challenge, with wide variability in its presentation depending on the subtype, leading to diagnostic delay and high mortality. Improvements are needed in the early diagnosis and treatment of these patients.

Validation of the usefulness of 2-dimensional strain parameters to exclude acute rejection after heart transplantation: a multicenter study.

INTRODUCTION AND OBJECTIVES: Two-dimensional speckle-tracking echocardiography has emerged as a promising alternative to endomyocardial biopsy to rule out acute cellular rejection after orthotopic heart transplantation (OHT) in single center studies. In an original cohort, 15.5% and 17% of cutoff points for left ventricular global longitudinal strain (LVGLS) and free-wall right ventricular longitudinal strain, respectively, achieved 100% negative predictive value to exclude moderate or severe acute cellular rejection (ACR ≥ 2R). Our objective was to demonstrate the usefulness of speckle-tracking and validate these cutoff points in an external cohort. METHODS: A prospective, multicenter study that included patients who were monitored during their first year after OHT was conducted. Echocardiographic studies analyzed by local investigators were compared with simultaneous paired endomyocardial biopsies samples. RESULTS: A total of 501 endomyocardial biopsy-echocardiographic studies were included in 99 patients. ACR≥2R was present in 7.4% of samples. LVGLS and free-wall right ventricular longitudinal strain were significantly reduced during ACR≥2R on univariate analysis. On multivariate analysis, LVGLS was independently associated with the presence of ACR≥2R. The original cutoff points demonstrated a negative predictive value of 94.3% to exclude ACR≥2R. CONCLUSIONS: This study maintained a strong negative predictive value to exclude ACR≥2R after OHT and LVGLS was independently associated with the presence of ACR≥2R. We propose the use of speckle-tracking, especially LVGLS, as part of the noninvasive diagnosis and management of ACR.

Multiparametric Echocardiography Scores for the Diagnosis of Cardiac Amyloidosis.

OBJECTIVES: This study aimed to investigate the accuracy of a broad range of echocardiographic variables to develop multiparametric scores to diagnose CA in patients with proven light chain (AL) amyloidosis or those with increased heart wall thickness who had amyloid was suspected. We also aimed to further characterize the structural and functional changes associated with amyloid infiltration. BACKGROUND: Cardiac amyloidosis (CA) is a serious but increasingly treatable cause of heart failure. Diagnosis is challenging and frequently unclear at echocardiography, which remains the most often used imaging tool. METHODS: We studied 1,187 consecutive patients evaluated at 3 referral centers for CA and analyzed morphological, functional, and strain-derived echocardiogram parameters with the aim of developing a score-based diagnostic algorithm. Cardiac amyloid burden was quantified by using extracellular volume measurements at cardiac magnetic resonance. RESULTS: A total of 332 patients were diagnosed with AL amyloidosis and 339 patients with transthyretin CA. Concentric remodeling and strain-derived parameters displayed the best diagnostic performance. A multivariable logistic regression model incorporating relative wall thickness, E wave/e' wave ratio, longitudinal strain, and tricuspid annular plane systolic excursion had the greatest diagnostic performance in AL amyloidosis (area under the curve: 0.90; 95% confidence interval: 0.87 to 0.92), whereas the addition of septal apical-to-base ratio yielded the best diagnostic accuracy in the increased heart wall thickness group (area under the curve: 0.80; 95% confidence interval: 0.85 to 0.90). CONCLUSIONS: Specific functional and structural parameters characterize different burdens of CA deposition with different diagnostic performances and enable the definition of 2 scores that are sensitive and specific tools with which diagnose or exclude CA.

Two-Dimensional Speckle Tracking Echocardiography in Heart Transplant Patients: Two-Year Follow-Up of Right and Left Ventricular Function.

BACKGROUND: Evolution of left and right ventricular (LV and RV) function after heart transplantation (HT) has not been well described. Our objective was to evaluate the evolution of echocardiographic parameters of both ventricles along the first 2 years after HT. METHODS: We followed 31 HT recipients with serial echocardiograms for up to 2 years. Echocardiograms with AR ≥2R were excluded. We analyzed LV global longitudinal strain (LV GLS) by speckle tracking in 12 segments in four- and two-chamber views and RV global longitudinal strain (RV GLS) in four-chamber view. Control group included 25 healthy volunteers. RESULTS: Even though LVEF was preserved, LV GLS was reduced early post-HT (-17.7 ± 3.0 in HT vs. -20.7 ± 2.8 in controls, P = 0.02), improving progressively until its complete normalization 2 years after HT (-20.0 ± 3.7 vs. -20.7 ± 2.8, P = 0.60). TAPSE was impaired in the early post-HT period and increased progressively (11.9 ± 2.9 mm at baseline vs. 19.0 ± 3.6 mm at 2 years, P < 0.001). RV GLS rose during follow-up as well (-17.4 ± 3.5 at baseline vs. -22.6 ± 3.3 at 2 years, P = 0.001), reaching normal values 1 year after HT. CONCLUSION: In this series of HT recipients with uneventful postoperative course, LV and RV GLS values were significantly reduced early after HT and improved progressively until their complete normalization two and 1 year after HT, respectively. This is the first study to show a full recovery of LV and RV deformation parameters and offers "normal" strain values that, if confirmed in larger studies, could be useful for monitoring the evolution of HT recipients.

Usefulness of Two-Dimensional Strain Parameters to Diagnose Acute Rejection after Heart Transplantation.

BACKGROUND: Acute cellular rejection (ACR) is still a relevant complication after orthotopic heart transplantation. The diagnosis of ACR is based on endomyocardial biopsy (EMB). Recent advances in two-dimensional strain imaging may allow early noninvasive detection of ACR. The objective of this study was to analyze the usefulness of conventional and new echocardiographic parameters to exclude ACR after orthotopic heart transplantation. METHODS: Thirty-four consecutive adult heart transplant recipients admitted to a single center between January 2010 and December 2012 for orthotopic heart transplantation were prospectively included. A total of 235 pairs of EMB and echocardiographic examination were performed. A median of seven studies per patient (interquartile range, six to eight studies per patient) were performed during the first year of follow-up. Classic echocardiographic parameters; speckle-tracking-derived left ventricular (LV) longitudinal, radial, and circumferential strain; and global and free wall right ventricular (RV) longitudinal strain were analyzed. RESULTS: ACR was detected in 26.4% of EMB samples (n = 62); 5.1% (n = 12) required specific treatment (ACR degree ≥ 2R). Lower absolute values of global LV longitudinal strain and free wall RV longitudinal strain were present in patients with ACR degree ≥ 2R compared with those without ACR (13.7 ± 2.7% vs 17.8 ± 3.4% and 16.6 ± 3.6% vs 23.3 ± 5.2%, respectively). An average LV longitudinal strain < 15.5% had 85.7% sensitivity, 81.4% specificity, 98.8% negative predictive value, 25.0% positive predictive value, and 81.7% accuracy for the presence of ACR degree ≥ 2R. Free wall RV longitudinal strain < 17% had 85.7% sensitivity, 91.1% specificity, 98.8% negative predictive value, 42.9% positive predictive value, and 90.7% accuracy for ACR degree ≥ 2R. Both variables were normal in 106 echocardiograms (57.6%); none of these patients presented with ACR degree ≥ 2R. CONCLUSIONS: The combination of two new echocardiographic measures, global LV and RV free wall longitudinal strain, may be able to identify a group of heart transplant patients who are unlikely to have ACR. If these findings are confirmed independently, it may be possible to use LV and RV strain measures as reliable tools to exclude ACR and to reduce the burden of repeated EMB.