RESUMO
BACKGROUND: The out-of-hospital cardiac arrest (OHCA) in the young may be associated with a genetic predisposition which is relevant even for genetic counseling of relatives. The identification of genetic variants depends on the availability of intact genomic DNA. DNA from autopsy may be not available due to low autopsy frequencies or not suitable for high-throughput DNA sequencing (NGS). The emergency medical service (EMS) plays an important role to save biomaterial for subsequent molecular autopsy. It is not known whether the DNA integrity of samples collected by the EMS is better suited for NGS than autopsy specimens. MATERIAL AND METHODS: DNA integrity was analyzed by standardized protocols. Fourteen blood samples collected by the EMS and biomaterials from autopsy were compared. We collected 172 autopsy samples from different tissues and blood with postmortem intervals of 14-168 h. For comparison, DNA integrity derived from blood stored under experimental conditions was checked against autopsy blood after different time intervals. RESULTS: DNA integrity and extraction yield were higher in EMS blood compared to any autopsy tissue. DNA stability in autopsy specimens was highly variable and had unpredictable quality. In contrast, collecting blood samples by the EMS is feasible and delivered comparably the highest DNA integrity. CONCLUSIONS: Isolation yield and DNA integrity from blood samples collected by the EMS is superior in comparison to autopsy specimens. DNA from blood samples collected by the EMS on scene is stable at room temperature or even for days at 4 °C. We conclude that the EMS personnel should always save a blood sample of young fatal OHCA cases died on scene to enable subsequent genetic analysis.
Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Humanos , Autopsia , Serviços Médicos de Emergência/métodos , MorteRESUMO
OBJECTIVES: Left atrial appendage (LAA) amputation concomitant to coronary artery bypass grafting (CABG) has become an increasingly performed technique in patients with atrial fibrillation (AF) or with sinus rhythm and a CHA2DS2-VASc score ≥2. However, LAA amputation has come under suspicion to cause postoperative atrial fibrillation (POAF) due to left atrial (LA) dilation. This study aims to assess this assumption in patients undergoing CABG in off-pump technique with and without amputation of the LAA. METHODS: Patients who underwent isolated CABG in off-pump technique without history of AF were retrospectively examined. Cohorts were divided according to the concomitant execution of LAA amputation. LA volume was measured by transthoracic echocardiography and rhythm was analyzed by electrocardiography, medication protocol, and visit documentation. Propensity score (PS) matching was performed based on 20 preoperative risk variables to correct for selection bias. RESULTS: A total of 1,522 patients were enrolled, with 1,267 in the control group and 255 in the LAA amputation group. Occurrence of POAF was compared in 243 PS-matched patient pairs. Neither the unmatched cohort (odds ratio [OR] 0.82; 95% confidence interval or CI [0.61; 1.11], p = 0.19) nor the PS-matched cohort (OR 0.94; 95% CI [0.62; 1.41], p = 0.75) showed significant differences in POAF occurrence. Subgroup analysis of sex, use of ß-blockers, pulmonary disease, ejection fraction, and CHA2DS2-VASc-Score also showed no tendencies. LA volume did not change significantly (p = 0.18, 95% CI [-0.29; 1.51]). CONCLUSION: Surgical amputation of the LAA concomitant to CABG did not lead to LA dilation and has no significant impact on the occurrence of POAF.
Assuntos
Apêndice Atrial , Fibrilação Atrial , Humanos , Apêndice Atrial/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Ponte de Artéria Coronária/efeitos adversos , Amputação Cirúrgica , Fatores de RiscoRESUMO
Cardiac lipomas are the second most common cardiac tumors. They are usually asymptomatic and diagnosed as incidental findings. We describe a 71-year-old patient with a tumor in the right atrium. In echocardiography and MRI scan, the diagnosis of a cardiac lipoma was suspected. Moreover, MRI demonstrated continuity of pericardial fat and the tumor in the right atrium by infolding of the atrial wall and epicardial adipose tissue in the space between the atrial walls, which might be a hint for the Waterstone groove hypothesis. An operative resection was performed which confirmed the suspected diagnosis.
Assuntos
Neoplasias Cardíacas , Lipoma , Humanos , Idoso , Resultado do Tratamento , Lipoma/complicações , Lipoma/diagnóstico por imagem , Átrios do Coração/patologia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , EcocardiografiaRESUMO
PURPOSE: Time of drug administration may significantly influence its effect. The aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients. METHODS: All patients (n = 114) had been diagnosed with coronary heart disease and arterial hypertension prior to the enrolment and had been treated with 75 mg per day of ASA in the morning. The patients were randomly assigned to one of the two study groups receiving 75 mg of ASA per day in a single antiplatelet therapy for 3 months in the morning (n = 58) or in the evening (n = 56). The control group (n = 61) consisted of patients with arterial hypertension but without coronary heart disease, not receiving ASA. In all the patients, during each visit, clinical blood pressure (BP) and ambulatory blood pressure measurements (ABPM) were performed. RESULTS: There was a significant reduction in 24-h BP and blood pressure at night in the ASA group evening group compared with the ASA morning group and the control group. CONCLUSIONS: The present study demonstrated that compared with the use of ASA in the morning, its administration in the evening may lead to favourable drop in the ABPM and an improvement of the diurnal profile in the high-risk group of cardiovascular patients who are not naïve to ASA.
Assuntos
Anti-Hipertensivos/administração & dosagem , Aspirina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Doença das Coronárias/tratamento farmacológico , Hipertensão/tratamento farmacológico , Idoso , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RiscoRESUMO
AIMS: We aimed to unravel the genetic, molecular and cellular pathomechanisms of DSC2 truncation variants leading to arrhythmogenic cardiomyopathy (ACM). METHODS AND RESULTS: We report a homozygous 4-bp DSC2 deletion variant c.1913_1916delAGAA, p.Q638LfsX647hom causing a frameshift carried by an ACM patient. Whole exome sequencing and comparative genomic hybridization analysis support a loss of heterozygosity in a large segment of chromosome 18 indicating segmental interstitial uniparental isodisomy (UPD). Ultrastructural analysis of the explanted myocardium from a mutation carrier using transmission electron microscopy revealed a partially widening of the intercalated disc. Using qRT-PCR we demonstrated that DSC2 mRNA expression was substantially decreased in the explanted myocardial tissue of the homozygous carrier compared to controls. Western blot analysis revealed absence of both full-length desmocollin-2 isoforms. Only a weak expression of the truncated form of desmocollin-2 was detectable. Immunohistochemistry showed that the truncated form of desmocollin-2 did not localize at the intercalated discs. In vitro, transfection experiments using induced pluripotent stem cell derived cardiomyocytes and HT-1080 cells demonstrated an obvious absence of the mutant truncated desmocollin-2 at the plasma membrane. Immunoprecipitation in combination with fluorescence measurements and Western blot analyses revealed an abnormal secretion of the truncated desmocollin-2. CONCLUSION: In summary, we unraveled segmental UPD as the likely genetic reason for a small homozygous DSC2 deletion. We conclude that a combination of nonsense mediated mRNA decay and extracellular secretion is involved in DSC2 related ACM.
Assuntos
Arritmias Cardíacas/genética , Cardiomiopatias/genética , Desmocolinas/genética , Deleção de Genes , Dissomia Uniparental/genética , Sequência de Aminoácidos , Arritmias Cardíacas/complicações , Sequência de Bases , Cardiomiopatias/complicações , Linhagem Celular Tumoral , Desmocolinas/química , Desmocolinas/metabolismo , Feminino , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Miocárdio/patologia , Miocárdio/ultraestrutura , Miócitos Cardíacos/metabolismo , LinhagemRESUMO
BACKGROUND: The clinical profile of left ventricular assist device (LVAD) candidates is rapidly changing, with increasing proportion of patients in more stable clinical conditions. However, early postoperative right ventricular failure (eRVF) is still one of the cornerstones associated with increased mortality and the preoperative recognition of associated risk factors remains challenging. The aim of this study was to identify predictive parameters for eRVF after LVAD implantation in patients with preoperative intermediate Intermacs (InM) risk profile 3-5. METHODS: Preoperative laboratory, echocardiography, and right heart catheterization data collected from 80 patients with InM profile 3-5 before LVAD implantation were retrospectively tested with respect to their ability to predict the risk for eRVF after the implantation of a continuous-flow LVAD. RESULTS: Preoperative higher bilirubin and blood urea nitrogen (BUN) levels, higher Model for End-stage Liver Disease score, lower estimated glomerular filtration rate, and higher central venous pressure to pulmonary capillary wedge pressure ratio (CVP/PCWP) were associated to higher risk of eRVF. Regarding the echocardiographic assessment, higher end diastolic linear dimensions of the RV, higher basal end diastolic RV linear dimension to LV ratio, severe tricuspid regurgitation, lower tricuspid annular plane systolic excursion, and lower RV fractional area contraction identified patients with higher risk for eRVF. In the multivariable analysis, a CVP/CPWP > 0.55 (odds ratio [OR]: 4, 95% confidence interval [CII]: 1.4-11.8;P = .01) and BUN > 44.5 mg/dL (OR: 6.6, 95% CI: 1.51-23; P = .011) independently predicted the risk of eRVF. CONCLUSION: Preoperative BUN > 44.5 mg/dL and CVP/PCWP > 0.55 are associated to an increased risk of eRVF following LVAD implantation in intermediate InM patients.
Assuntos
Insuficiência Cardíaca/etiologia , Coração Auxiliar/efeitos adversos , Disfunção Ventricular Direita/etiologia , Nitrogênio da Ureia Sanguínea , Progressão da Doença , Ventrículos do Coração , Humanos , Período Pré-Operatório , Pressão Propulsora Pulmonar , Fatores de RiscoRESUMO
Restrictive cardiomyopathy (RCM) is a rare heart disease characterized by diastolic dysfunction and atrial enlargement. The genetic etiology of RCM is not completely known. We identified by a next-generation sequencing panel the novel CRYAB missense mutation c.326A>G, p.D109G in a small family with RCM in combination with skeletal myopathy with an early onset of the disease. CRYAB encodes αB-crystallin, a member of the small heat shock protein family, which is highly expressed in cardiac and skeletal muscle. In addition to in silico prediction analysis, our structural analysis of explanted myocardial tissue of a mutation carrier as well as in vitro cell transfection experiments revealed abnormal protein aggregation of mutant αB-crystallin and desmin, supporting the deleterious effect of this novel mutation. In conclusion, CRYAB appears to be a novel RCM gene, which might have relevance for the molecular diagnosis and the genetic counseling of further affected families in the future.
Assuntos
Cardiomiopatia Restritiva/diagnóstico , Cardiomiopatia Restritiva/genética , Cadeia B de alfa-Cristalina/genética , Adulto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação de Sentido Incorreto/genética , Linhagem , Adulto JovemRESUMO
AIMS: Coronary artery disease accounts for the majority of sudden cardiac deaths (SCD) in the older population whereas cardiomyopathies and arrhythmogenic abnormalities predominate in younger SCD victims (<35 years) with a significant genetic component. The elucidation of the pathogenetic cause of death might be relevant for the prevention of further deaths within affected families. Aim of this study was to determine the portion of underlying genetic heart diseases among unexplained putative SCD cases from a large German forensic department. METHODS AND RESULTS: We included 10 forensic cases of sudden unexplained death (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was analysed by next generation panel sequencing of 174 candidate genes for channelopathies and cardiomyopathies. Cardiological examinations, genetic counselling, and subsequent genetic testing were offered to all affected families. We identified within 1 year 10 cases of SUD among 172 forensic cases. Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD cases. Subsequent selective screening of family members revealed two additional mutation carriers. CONCLUSION: The study provides strong evidence that molecular genetics improves the post mortem diagnosis of fatal genetic heart diseases among SUD victims. Molecular genetics should be integrated in forensic and pathological routine practice.
Assuntos
Arritmias Cardíacas/genética , Análise Mutacional de DNA/métodos , Morte Súbita Cardíaca/etiologia , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Adulto , Fatores Etários , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Autopsia , Causas de Morte , Morte Súbita Cardíaca/patologia , Evolução Fatal , Feminino , Predisposição Genética para Doença , Alemanha , Humanos , Masculino , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVES: We investigated the impact of inodilators on the accuracy of E/e' ratio as a surrogate for pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure. SETTING: The ratio of early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity, E/e', and pulmonary artery occlusion pressure have been shown to be correlated. The validity of E/e' for predicting pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure was recently challenged, but the influence of inodilators was not taken into account, despite the reported influence of these drugs on left ventricular relaxation properties. PATIENTS AND INTERVENTION: Invasive hemodynamic monitoring and echocardiographic data were collected prospectively from 39 patients with decompensated end-stage systolic heart failure (92% male), aged 56 ± 13 years. These patients had dilated ventricles with a low cardiac index (1.9 ± 0.6 L/min/m) and high pulmonary artery occlusion pressure (22 ± 8 mm Hg), and 90% required inodilator support during hospitalization. MEASUREMENTS AND MAIN RESULTS: The correlation between septal E/e' and pulmonary artery occlusion pressure was good for examinations in the absence of inodilators (n = 21) (r = 0.7; p < 0.001), but no correlation was found when inodilators were used (n = 31). Lateral and mean E/e' were poorly correlated with pulmonary artery occlusion pressure, if at all, in both cases. CONCLUSIONS: By modifying ventricular relaxation properties and the influence of filling pressure on e', inodilator agents severely impair the correlation between E/e' and pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure.
Assuntos
Fármacos Cardiovasculares/farmacologia , Insuficiência Cardíaca/fisiopatologia , Adulto , Idoso , Velocidade do Fluxo Sanguíneo , Ecocardiografia , Ecocardiografia Doppler , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Pressão Propulsora PulmonarRESUMO
The aim of the study was to assess the occurrence of classic risk factors in the study group of patients with heart failure and to link them with the transcriptional activity of the examined genes: metalloproteinase 9 (MMP-9) and the tissue inhibitor of metalloproteinases 1 (TIMP-1). A total of 150 (100%) patients qualified for the study, including 80 (53.33%) patients with heart failure in the course of coronary artery disease, 40 (26.67%) with coronary artery disease without heart failure, and 30 (20.00%) in whom the presence of atherosclerotic changes in the coronary arteries was excluded. The material for molecular tests was peripheral blood collected from patients within the first 24 h of hospitalisation. A quantitative analysis of transcriptional activity was performed using the RT-qPCR technique. The most common classic risk factors among the patients in the study group were arterial hypertension (117; 78.00%) and overweight/obesity (102; 68%). In the group of patients with coronary artery disease and heart failure burdened with overweight/obesity, a significantly higher transcriptional activity of the metalloproteinase 9 (MMP-9) gene was found in comparison to patients who were not burdened with this risk factor. The analysis also showed the statistically significant higher transcriptional activity of the metalloproteinase 9 (MMP-9) gene in a group of patients with coronary artery disease and heart failure who smoked. The examined patients with heart failure due to myocardial ischemia were burdened with numerous cardiovascular risk factors, the most common of which were arterial hypertension, obesity/overweight, and hypercholesterolemia. A significant increase in the transcriptional activity of the metalloproteinase 9 (MMP-9) gene in the presence of risk factors (male sex, overweight/obesity, smoking) indicates another pathomechanism of their action and participation in the development and progression of heart failure during myocardial ischemia. There is a need for systematic information and educational activities promoting a healthy lifestyle with the elimination of modifiable risk factors for cardiovascular diseases.
RESUMO
Background: Right ventricular (RV) strain has provided valuable prognostic information for patients with cardiac amyloidosis (CA). However, the extent to which RV strain and strain rate can differentiate CA is not yet clinically established. CA underdiagnosis delays treatment strategies and exacerbates patient prognosis. Aims: Evaluation of cardiac magnetic resonance (CMR) quantified RV global and regional strain of CA and HCM patients along with CA subtypes. Methods: CMR feature tracking attained longitudinal, radial and circumferential global and regional strain in 47 control subjects (CTRL), 43 CA-, 20 hypertrophic cardiomyopathy- (HCM) patients. CA patients were subdivided in 21 transthyretin-related amyloidosis (ATTR) and 20 acquired immunoglobulin light chain (AL) patients. Strain data and baseline clinical parameters were statistically analysed with respect to diagnostic performance and discriminatory power between the different clinical entities. Results: Effective differentiation of CA from HCM patients was achieved utilizing global longitudinal (GLS: 16.5 ± 3.9% vs. -21.3 ± 6.7%, p = 0.032), radial (GRS: 11.7 ± 5.3% vs. 16.5 ± 7.1%, p < 0.001) and circumferential (GCS: -7.6 ± 4.0% vs. -9.4 ± 4.4%, p = 0.015) right ventricular strain. Highest strain-based hypertrophic phenotype differentiation was attained using GRS (AUC = 0.86). Binomial regression found right ventricular ejection fraction (RV-EF) (p = 0.017) to be a significant predictor of CA-HCM differentiation. CA subtypes had comparable cardiac strains. Conclusion: CMR-derived RV global strains and various regional longitudinal strains provide discriminative radiological features for CA-HCM differentiation. However, in terms of feasibility, cine-derived RV-EF quantification may suffice for efficient differential diagnostic support.
RESUMO
INTRODUCTION: Drug therapy to reduce the regurgitation fraction (RF) of high-grade aortic regurgitation (AR) by increasing heart rate (HR) is generally recommended. However, chronic HR reduction in HFREF patients can significantly improve aortic compliance and thereby potentially decrease RF. To clarify these contrasts, we examined the influence of HR, aortic compliance and stroke volume (SV) on RF in an ex vivo porcine model of severe AR. METHODS: Experiments were performed on porcine ascending aorta with aortic valves (n=12). Compliance was varied by inserting a Dacron graft close to the aortic valve. Both tube systems were connected to a left heart simulator varying HR and SV. AR was accomplished by punching a 0.3 cm2 hole in one aortic cusp. Flow, RF, SV and aortic pressure were measured, aortic compliance with transoesophageal ultrasound probes. RESULTS: Compliance of the aorta was significantly reduced after Dacron graft insertion (0.55%±0.21%/mm Hg vs 0.01%±0.007%/mm Hg, p<0.001, respectively). With increasing HR, RF was significantly reduced in each steady state of the native aorta (HR 40 bpm: 88%±7% vs HR 120 bpm: 42%±10%; p<0.001), but Dacron tube did not affect RF (HR 40 bpm: 87%±8%; p=0.79; HR 120 bpm: 42%±3%; p=0.86). Increasing SV also reduced RF independent of the stiff Dacron graft. CONCLUSION: Aortic compliance did not affect AR in the ex vivo porcine model of AR. RF was significantly reduced with increasing HR and SV. These results affirm that HR lowering and negative inotropic drugs should be avoided to treat severe AR.
Assuntos
Insuficiência da Valva Aórtica , Insuficiência Cardíaca , Humanos , Suínos , Animais , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/cirurgia , Frequência Cardíaca , Volume Sistólico , Polietilenotereftalatos , Aorta/diagnóstico por imagem , Aorta/cirurgiaRESUMO
OBJECTIVES: Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality. METHODS: The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort. RESULTS: In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2- 5.5) vs 2 (2- 4); P < 0.001], received more right ventricular assist devices (RVAD) [32 (8%) vs 178 (5.5%); P = 0.038] and stayed longer in the intensive care unit post-LVAD implant [19 (8-35) vs 11(5-25); P < 0.001]. Yet, there was no significant difference in the rate of RHF, 30-day, or 1-year mortality. Also, in the matched cohort (357 patients taking levosimendan compared to an average of 622 controls across 20 imputations), we found no evidence for a difference in postoperative severe RHF, RVAD implant rate, length of stay in the intensive care unit or 30-day and 1-year mortality. CONCLUSIONS: In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted.
Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Adulto , Humanos , Coração Auxiliar/efeitos adversos , Simendana , Pontuação de Propensão , Estudos Retrospectivos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/cirurgia , Sistema de Registros , Resultado do TratamentoRESUMO
Left-atrial (LA) strain is the result of complex hemodynamics, which may be better characterized using a multiparametric approach. Cardiovascular magnetic resonance (CMR) feature tracking was used to perform a comprehensive LA strain assessment of 183 enrolled healthy volunteers (11-70 years, 97 females, median 32.9 ± 28.3 years). Novel strain dependencies were assessed using multi-parametric regression (MPR) analyses. LA volumetric data, left ventricular strain, transmitral and pulmonary venous blood flow parameters were utilized to create clusters for MPR of all subjects and a heart rate controlled subgroup (pulse: 60-75/min, N = 106). The LA reservoir(r) and conduit(c) strains of the total cohort were significantly elevated (p ≤ 0.001) in women (r: 49.7 ± 12.9%, c: 32.0 ± 11.0%) compared to men (r: 42.9 ± 11.4%, c: 26.1 IQ 10.5%). In contrast, there were no gender-specific differences (p > 0.05) for subgroup LA reservoir, conduit and booster(b) strains (all, r: 47.3 ± 12.7%; c: 29.0 IQ 15.5%; b: 17.6 ± 5.4%) and strain rates (all, 2.1 IQ 1.0 s-1; - 2.9 IQ 1.5 s-1; - 2.3 IQ 1.0 s-1). MPR found large effect sizes (|R2|≥ 0.26) for correlations between strain and various cardiac functional parameters. Largest effect size was found for the association between LA conduit strain and LA indexed booster volume, LA total ejection fraction, left ventricular global radial strain and E-wave (|R2|= 0.437). In addition to providing normal values for sex-dependent LA strain and strain rate, no gender differences were found with modified heart rate. MPR analyses of LA strain/strain rate and various cardiac functional parameters revealed that heart rate control improved goodness-of-fit for the overall model.
Assuntos
Função do Átrio Esquerdo , Imagem Cinética por Ressonância Magnética , Função do Átrio Esquerdo/fisiologia , Feminino , Átrios do Coração , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Volume SistólicoRESUMO
Background: Cardiac amyloidosis (CA) manifests in a hypertrophic phenotype with a poor prognosis, making differentiation from hypertrophic cardiomyopathy (HCM) challenging and delaying early treatment. The extent to which magnetic resonance imaging (MRI) quantifies the right atrial strain (RAS) and strain rate (RASR), providing valuable diagnostic information, is not yet clinically established. Aims: This study assesses diagnostic differences in the longitudinal RAS and RASR between CA and HCM patients, control subjects (CTRL) and CA subtypes in addition to the impact of atrial fibrillation (AF) on the right atrial function in CA patients. The RAS and RASR of tricuspid regurgitation (TR) patients are used to assess the potential for diagnostic overlap. Methods: RAS and RASR quantification was conducted via MRI feature-tracking for biopsy-confirmed CA patients with subtypes identified. Strain parameters were compared for CTRL, HCM and TR patients. Post hoc testing identified intergroup differences. Results: In total, 41 CA patients were compared to 47 CTRL, 20 HCM and 31 TR patients. Reservoir (R), conduit and booster RAS and RASRs allow for significant differentiation (p < 0.001) between CA and HCM patients (R: 10.6 ± 14.3% vs. R: 33.5 ± 16.3%) and CTRL (R: 44.6 ± 15.7%). Booster and reservoir RAS and RASRs qualified as reliable diagnostic tests (AUC > 0.8). CA patients with AF, in contrast to sinus rhythm, demonstrated a significantly impaired reservoir RAS and RASR and booster RASR. The discriminative power of RAS for CA vs. TR was insufficient (R: 10.6% ± 14.3% vs. 7.0% ± 6.0%, p = 0.069). Differentiation between 21 transthyretin and 20 light-chain amyloidosis subtypes was not achievable (R: 0.7% ± 1.0% vs. 0.7% ± 1.0%, p = 0.827). Conclusion: The MRI-derived RAS and RASR are impaired in CA patients and may support noninvasive differentiation between CA, HCM and CTRL.
RESUMO
BACKGROUND: This study challenges state-of-the-art cardiac amyloidosis (CA) diagnostics by feeding multi-chamber strain and cardiac function into supervised machine (SVM) learning algorithms. METHODS: Forty-three CA (32 males; 79 years (IQR 71; 85)), 20 patients with hypertrophic cardiomyopathy (HCM, 10 males; 63.9 years (±7.4)) and 44 healthy controls (CTRL, 23 males; 56.3 years (IQR 52.5; 62.9)) received cardiovascular magnetic resonance imaging. Left atrial, right atrial and right ventricular strain parameters and cardiac function generated a 41-feature matrix for decision tree (DT), k-nearest neighbor (KNN), SVM linear and SVM radial basis function (RBF) kernel algorithm processing. A 10-feature principal component analysis (PCA) was conducted using SVM linear and RBF. RESULTS: Forty-one features resulted in diagnostic accuracies of 87.9% (AUC = 0.960) for SVM linear, 90.9% (0.996; Precision = 94%; Sensitivity = 100%; F1-Score = 97%) using RBF kernel, 84.9% (0.970) for KNN, and 78.8% (0.787) for DT. The 10-feature PCA achieved 78.9% (0.962) via linear SVM and 81.8% (0.996) via RBF SVM. Explained variance presented bi-atrial longitudinal strain and left and right atrial ejection fraction as valuable CA predictors. CONCLUSION: SVM RBF kernel achieved competitive diagnostic accuracies under supervised conditions. Machine learning of multi-chamber cardiac strain and function may offer novel perspectives for non-contrast clinical decision-support systems in CA diagnostics.
RESUMO
INTRODUCTION AND OBJECTIVES: The effect of a centrifugal continuous-flow left ventricular assist device (cfLVAD) on hemodynamic left ventricular unloading (HLVU) and the clinical conditions that interfere with hemodynamic optimization are not well defined. METHODS: We retrospectively evaluated the likelihood of incomplete HLVU, defined as high pulmonary capillary wedge pressure (hPCWP)> 15mmHg in 104 ambulatory cfLVAD patients when the current standard recommendations for cfLVAD rotor speed setting were applied. We also evaluated the ability of clinical, hemodynamic and echocardiographic variables to predict hPCWP in ambulatory cfLVAD patients. RESULTS: Twenty-eight percent of the patients showed hPCWP. The variables associated with a higher risk of hPCWP were age, central venous pressure, absence of treatment with renin-angiotensin-aldosterone system inhibitors, and brain natriuretic peptide levels. Patients with optimal HLVU had a 15.2±14.7% decrease in postoperative indexed left ventricular end-diastolic diameter compared with 8.9±11.8% in the group with hPCWP (P=.041). Independent predictors of hPCWP included brain natriuretic peptide and age. Brain natriuretic peptide <300 pg/mL predicted freedom from hPCWP with a negative predictive value of 86% (P <.0001). CONCLUSIONS: An optimal HLVU can be achieved in up to 72% of the ambulatory cfLVAD patients when the current standard recommendations for rotor speed setting are applied. Age, central venous pressure and therapy with renin-angiotensin-aldosteron system inhibitors had a substantial effect on achieving this goal. Brain natriuretic peptide levels and the magnitude of reverse left ventricular remodeling seem to be useful noninvasive tools to evaluate HLVU in patients with functioning cfLVAD.
Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/cirurgia , Hemodinâmica , Humanos , Peptídeo Natriurético Encefálico , Estudos RetrospectivosRESUMO
OBJECTIVES: The development of late-onset right ventricular failure (LoRVF) that occurs months after a continuous-flow left ventricular assist device (LVAD) is implanted is a clinical problem that warrants investigation. Our goal was to study the incidence, clinical manifestations and prognosis of LoRVF in a population of patients who received an LVAD as bridge to transplantation. METHODS: Data were analysed from 97 consecutive patients who received an LVAD as bridge to transplantation and underwent a right heart catheterization at least 3 months after receiving an LVAD implantation. LoRVF was defined if both haemodynamic criteria of a central venous pressure >16 mmHg and a cardiac index <2.3 l/min/m2 were present. Clinical and echocardiographic variables, hospitalizations for heart failure and survival were compared between patients with and without LoRVF. RESULTS: LoRVF was diagnosed in 13% of patients after a median time of 11 months. Patients with LoRVF presented preoperative worse right ventricular (RV) dilatation and severe tricuspid regurgitation. LORVF was also associated with postoperative RV dilatation, moderate to severe tricuspid regurgitation and lower tricuspid annular plane systolic excursion. LoRVF resulted in increased brain natriuretic peptide levels and the need for diuretics, lower haemoglobin levels and a higher rate of atrial fibrillation and gastrointestinal bleeding. The rate of hospitalizations for heart failure in patients with LoRVF was 46%, and 15% required an urgent transplantation due to refractory RV failure. LoRVF decreased global survival and survival free from hospitalizations for heart failure (P < 0.0001). CONCLUSIONS: LoRVF after the implantation of an LVAD as bridge to transplantation is associated with higher morbidity and lower survival. The results suggest that the routine use of a right heart catheterization and transthoracic echocardiography may contribute to an early diagnosis before further severe complications due to refractory RV failure might occur. ID NUMBER OF THE IRB APPROVAL: AZ-2019-521 on 10 July 2019.
Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Ecocardiografia , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/epidemiologia , Disfunção Ventricular Direita/etiologiaRESUMO
Currently, little is known about the genetic background of restrictive cardiomyopathy (RCM). Herein, we screened an index patient with RCM in combination with atrial fibrillation using a next generation sequencing (NGS) approach and identified the heterozygous mutation DES-c.735G>C. As DES-c.735G>C affects the last base pair of exon-3, it is unknown whether putative missense or splice site mutations are caused. Therefore, we applied nanopore amplicon sequencing revealing the expression of a transcript without exon-3 in the explanted myocardial tissue of the index patient. Western blot analysis verified this finding at the protein level. In addition, we performed cell culture experiments revealing an abnormal cytoplasmic aggregation of the truncated desmin form (p.D214-E245del) but not of the missense variant (p.E245D). In conclusion, we show that DES-c.735G>C causes a splicing defect leading to exon-3 skipping of the DES gene. DES-c.735G>C can be classified as a pathogenic mutation associated with RCM and atrial fibrillation. In the future, this finding might have relevance for the genetic understanding of similar cases.
RESUMO
OBJECTIVES: Data on the impact and course of uncorrected tricuspid regurgitation (TR) during left ventricular assist device (LVAD) implantation are scarce and inconsistent. This study explores the clinical impact and natural course of uncorrected TR in patients after LVAD implantation. METHODS: The European Registry for Patients with Mechanical Circulatory Support was used to identify adult patients with LVAD implants without concomitant tricuspid valve surgery. A mediation model was developed to assess the association of TR with 30-day mortality via other risk factors. Generalized mixed models were used to model the course of post-LVAD TR. Joint models were used to perform sensitivity analyses. RESULTS: A total of 2496 procedures were included (median age: 56 years; men: 83%). TR was not directly associated with higher 30-day mortality, but mediation analyses suggested an indirect association via preoperative elevated right atrial pressure and creatinine (P = 0.035) and bilirubin (P = 0.027) levels. Post-LVAD TR was also associated with increased late mortality [hazard ratio 1.16 (1.06-1.3); P = 0.001]. On average, uncorrected TR diminished after LVAD implantation. The probability of having moderate-to-severe TR immediately after an implant in patients with none-to-mild TR pre-LVAD was 10%; in patients with moderate-to-severe TR pre-LVAD, it was 35% and continued to decrease in patients with moderate-to-severe TR pre-LVAD, regardless of pre-LVAD right ventricular failure or pulmonary hypertension. CONCLUSIONS: Uncorrected TR pre-LVAD and post-LVAD is associated with increased early and late mortality. Nevertheless, on average, TR diminishes progressively without intervention after an LVAD implant. Therefore, these data suggest that patient selection for concomitant tricuspid valve surgery should not be based solely on TR grade.