Symptom burden, psychosocial distress and palliative care needs in heart failure - A cross-sectional explorative pilot study.

BACKGROUND: Beyond guideline-directed treatments aimed at improving cardiac function and prognosis in heart failure (HF), patient-reported outcomes have gained attention. PURPOSE: Using a cross-sectional approach, we assessed symptom burden, psychosocial distress, and potential palliative care (PC) needs in patients with advanced stages of HF. METHODS: At a large tertiary care center, we enrolled HF patients in an exploratory pilot study. Symptom burden and psychosocial distress were assessed using the MIDOS (Minimal Documentation System for Patients in PC) questionnaire and the Distress Thermometer (DT), respectively. The 4-item Patient Health Questionnaire (PHQ-4) was used to screen for anxiety and depression. To assess PC needs, physicians used the "Palliative Care Screening Tool for HF Patients". RESULTS: We included 259 patients, of whom 137 (53%) were enrolled at the Heart Failure Unit (HFU), and 122 (47%) at the outpatient clinic (OC). Mean age was 63 years, 72% were male. New York Heart Association class III or IV symptoms were present in 56%. With a mean 5-year survival 64% (HFU) vs. 69% (OC) calculated by the Seattle Heart Failure Model, estimated prognosis was comparatively good. Symptom burden (MIDOS score 8.0 vs. 5.4, max. 30 points, p < 0.001) and level of distress (DT score 6.0 vs. 4.8, max. 10 points, p < 0.001) were higher in hospitalised patients. Clinically relevant distress was detected in the majority of patients (HFU 76% vs. OC 57%, p = 0.001), and more than one third exhibited at least mild symptoms of depression or anxiety. Screening for PC needs revealed 82% of in- and 52% of outpatients fulfil criteria for specialized palliative support. CONCLUSION: Despite a good prognosis, we found multiple undetected and unaddressed needs in an advanced HF cohort. This study's tools and screening results may help to early explore these needs, to further improve integrated HF care.

Comparison of Cine-MRI and Transthoracic Echocardiography for the Assessment of Aortic Root Diameters in Patients with Suspected Marfan Syndrome.

PURPOSE: Patients with Marfan syndrome require repeated imaging for monitoring of aortic root aneurysms. Therefore, we evaluated the agreement and reproducibility of cine-MRI and echocardiography measurements of the sinuses of Valsalva in patients with suspected Marfan syndrome. MATERIALS AND METHODS: 51 consecutive patients with suspected Marfan syndrome were prospectively examined using cine-MRI and echocardiography. Two readers independently measured aortic root diameters at the level of the sinuses of Valsalva in both cine-MRI and echocardiography. Statistics included intraclass correlation coefficient, Pearson correlation coefficient, Bland-Altman analysis, and two-sided t-test. RESULTS: In 38 of the 51 individuals (74.5 %), the diagnosis of Marfan syndrome was established according to the criteria of the Ghent-2 nosology. Cine-MRI measurements of the sinuses of Valsalva revealed a strong correlation with echocardiography (r = 0.929), but a statistically significant bias of -1.0  mm (p < 0.001). The mean absolute diameter for sinuses of Valsalva obtained by cine-MRI was 32.3  ±  5.8 mm as compared to 33.4  ±  5.4 mm obtained by echocardiography. Interobserver agreement of measurements of the sinuses of Valsalva was higher for cine-MRI than for echocardiography (p = 0.029). CONCLUSION: Despite small, but statistically significant differences in terms of agreement and reproducibility, cine-MRI and echocardiographic measurements of aortic root diameters provide comparable results without a significant clinical difference. Therefore both techniques may be used for monitoring of the aortic root in patients with Marfan syndrome.

Comprehensive analysis of dural ectasia in 150 patients with a causative FBN1 mutation.

The purpose of this study was to perform a comprehensive study of dural ectasia (DE) related to FBN1 mutations. We performed a database analysis of two German metropolitan regions of 150 patients (68 men, 82 women; mean age 35 ± 16 years). All patients had a FBN1 mutation and underwent dural magnetic resonance imaging. Age was <16 years in 20, 16-25 in 27, 26-35 in 67, and >35 in 36 patients. Prevalence of dural ectasia was 89% with criteria of Oosterhof and Habermann, 83% with Fattori, 78% with Lundby, and 59% with Ahn. DE was less frequent in patients <16 years with Ahn and Fattori. DE related to skeletal manifestations with all criteria, to aortic Z-scores and mitral valve prolapse with criteria of Habermann and Lundby, and to age with criteria of Fattori. The Fattori-grade of DE increased with age, aortic Z-scores, and skeletal score points. There was no consistent relationship of DE with any type of FBN1 mutation. DE is frequent in patients with FBN1 mutations irrespective of age and its severity increases during life. Criteria of Oosterhof and Habermann yielded most consistent diagnostic results. DE relates to skeletal involvement, aortic Z-scores, and mitral valve prolapse.

A simple clinical model to estimate the probability of Marfan syndrome.

BACKGROUND: Marfan syndrome is a heritable connective tissue disease. Definitive diagnosis is complex, and requires sequencing of a large gene, FBN1. AIM: We aimed to develop a simple model to estimate the pre-test probability of Marfan syndrome. DESIGN: Prospective cross-sectional study. METHODS: We applied diagnostic standards for definitive diagnosis or exclusion of Marfan syndrome in 329 consecutive persons. In 208 persons with random assignment to our derivation group, we performed multivariate logistic regression to assess 14 clinical variables for inclusion in a prediction model with derivation of score points from the estimated coefficients. We created cut-offs to classify low, moderate and high probability of Marfan syndrome. For validation, we applied the model to the remaining 121 persons. RESULTS: We identified seven variables for inclusion in the final model, where we assigned four score points to ectopia lentis, two points to a family history of Marfan syndrome, and one point to previous thoracic aortic surgery, to pectus excavatum, to a wrist and thumb sign, to previous pneumothorax, and to skin striae. In the derivation group 12, 42 and 92% of persons with low (≤1 point), moderate (>1-3.5 points) or high pre-test probability (>3.5 points) had Marfan syndrome, compared to 12, 57 and 91%, respectively, in the validation group. Positive likelihood ratios were 13.96 and 8.54 in the high probability group of the derivation and validation group, respectively. CONCLUSION: A simple prediction model provides evidence for Marfan syndrome. This model can be used to identify patients who require definitive diagnostic work-up.

Analysis of phenotype and genotype information for the diagnosis of Marfan syndrome.

Marfan syndrome is considered a clinical diagnosis. Three diagnostic classifications comprising first, Marfan genotype with a causative FBN1 gene mutation; second, Marfan phenotype with clinical criteria of the original Ghent nosology (Ghent-1); and third, phenotype with clinical criteria of its current revision (Ghent-2) in 300 consecutive persons referred for confirmation or exclusion of Marfan syndrome (150 men, 150 women aged 35 ± 13 years) were used. Sequencing of TGBR1/2 genes was performed in 128 persons without FBN1 mutation. Marfan genotype was present in 140, Ghent-1 phenotype in 139, and Ghent-2 phenotype in 124 of 300 study patients. Marfan syndrome was confirmed in 94 and excluded in 129 persons consistently by all classifications, but classifications were discordant in 77 persons. With combined genotype and phenotype information confirmation of Marfan syndrome was finally achieved in 126 persons by Ghent-1 and in 125 persons by Ghent-2 among 140 persons with Marfan genotype, and exclusion was accomplished in 139 persons by Ghent-1 and in 141 persons by Ghent-2 among 160 persons without Marfan genotype. In total, genotype information changed final diagnoses in 22 persons with Ghent-1, and in 32 persons with Ghent-2. It is concluded that genotype information is essential for diagnosis or exclusion of Marfan syndrome.

[Diagnosis and options for reconstructive heart valve surgery in the Marfan syndrome].

Marfan syndrome is a disorder of the connective tissue that is inherited in an autosomal-dominant fashion and that is caused by mutations in the gene coding for fibrillin-1, FBN1. Although complications of the syndrome may involve the eye, the lung and the skeleton, the high mortality of untreated cases results almost exclusively from cardiovascular complications, including aortic dissection, rupture and mitral valve regurgitation. The multiorgan involvement of many of these syndromes requires multidisciplinary expert centers that can increase the average life expectancy of affected patients from only 32 years to over 60 years. The present article both reviews classical standards of managing cardiovascular manifestations and highlights the surgical approach for aortic and mitral valve surgery in Marfan patients.

Dural ectasia in individuals with Marfan-like features but exclusion of mutations in the genes FBN1, TGFBR1 and TGFBR2.

Mutations in the genes FBN1, TGFBR1, and TGFBR2 can result in heritable connective tissue disorders comprising the Marfan syndrome and the Loeys-Dietz syndrome. Dural ectasia is a characteristic manifestation of both syndromes. However, dural ectasia has not yet been investigated in connective tissue disorders that are unrelated to mutations in the FBN1, TGFBR1 or TGFBR2 genes. Here, we assessed dural ectasia in 33 individuals both with typical manifestations of heritable connective tissue disease and in whom mutations in all three genes had been excluded. We identified 19 individuals with dural ectasia (58%), who exhibited major skeletal manifestations of the Marfan syndrome more frequently than the remaining 14 persons without dural ectasia (p = 0.06). Moreover, only persons with dural ectasia fulfilled clinical criteria of the Marfan syndrome (p = 0.01). Conversely, aortic aneurysm (12 patients; p = 0.8), aortic dissection (five patients; p = 0.1), spontaneous dissection of the carotid arteries (five patients; p = 1), and mitral valve prolapse (13 patients; p = 0.4) were similarly frequent irrespective of dural ectasia. We conclude that dural ectasia is a marker for connective tissue disease which coincides with skeletal rather than with cardiovascular manifestations, and which may involve currently uncharacterized pathogenetic mechanisms and syndromes.

Marfan syndrome and the evolving spectrum of heritable thoracic aortic disease: do we need genetics for clinical decisions?

Marfan syndrome (MFS) is a disorder of the connective tissue that is inherited in an autosomal dominant fashion and that is classically caused by mutations in the gene coding for fibrillin-1, FBN1. The high mortality of untreated MFS results almost exclusively from aortic complications such as aortic dissection and rupture. However, more than half of patients with Marfan-like features do not have MFS, but have other diseases including inherited aortic aneurysms and dissections (TAAD). We elucidate the increasing spectrum of syndromes associated with Marfan-like features and discuss the clinical implications of these diseases. We performed a systematic review to tabulate all known inherited diseases and syndromes carrying a risk for thoracic aortic disease. We discuss evidence that different syndromes with different causative genes and mutations have different prognoses and profiles of cardiovascular manifestations. We conclude that future decisions for optimized management of patients with inherited TAAD require a comprehensive clinical and genetic work-up.

[Improved analysis of left ventricular function using three-dimensional echocardiography]. / Verbesserte Beurteilung der linksventrikulären Funktion mittels 3D-Echokardiographie.

Left ventricular geometry and function are important pathophysiologic and prognostic parameters. However, especially in patients with cardiac pathologies left ventricular geometry can be complex. Quantification of left ventricular volumes using conventional two-dimensional echocardiography is only possible when simplifying assumptions of left ventricular geometry are made. In contrast three-dimensional echocardiography allows direct quantification of left ventricular volumes even in complex distortions of left ventricular shape. The availability of real-time three-dimensional echocardiography has brought this technique into clinical practice. Three-dimensional echocardiography is a technique that may be used as a routine echocardiographic method in the near future.

[Marfan syndrome: pathogenesis, phenotypes and diagnostic value, of various imaging techniques]. / Das Marfan-Syndrom: Pathogenese, Phänotypien und Stellenwert bildgebender Verfahren.

Marfan syndrome is a genetic disorder with autosomal dominant inheritance. It is caused by mutations in the fibrillin-1 gene and leads to different disease manifestations. Seventy-five percent of the affected individuals develop an aneurysm of the ascending aorta, 41 % suffer from aortic dissections, and 93 % die of cardiovascular diseases. Skeletal changes occur in two-thirds of the patients, and lens dislocation is observed in 60 to 80 %. Without treatment, the life expectancy is 32 +/- 16 years. However, Marfan patients can live up to 60 years if they receive optimal therapy. Early diagnosis of the disease and it 's life-threatening sequelae is the prerequisite for early therapy. Radiologic diagnostic techniques are of pivotal importance in this context as they allow the identification of major and minor disease manifestations and the detection of severe dilatations and aortic dissections at an early stage. This overview describes the radiologically detectable multiple changes seen in Marfan syndrome and explains the diagnostic value of various imaging techniques in the diagnosis and therapy of Marfan syndrome.