Identification of microdeletion and microduplication syndromes by chromosomal microarray in patients with intellectual disability with dysmorphism.

BACKGROUND: A retrospective analysis using chromosomal microarray in syndromic patients with intellectual disability from genetic clinics of a tertiary healthcare center in India was conducted. AIM: To identify the spectrum of chromosomal abnormalities detected on microarray analysis. SETTINGS AND DESIGN: Cases were identified among those with intellectual disability with dysmorphism attending genetic clinics of a tertiary care center. PATIENTS AND METHODS: All patients attending genetic clinics over a 3-year period were analyzed. Clinical profile and baseline investigations were noted on a predesigned proforma. Among the 65 studied cases, there were 12 cases suggested to be having Prader-Willi syndrome (PWS), 27 cases with DiGeorge/velocardiofacial syndrome (DGS), and 1 case with Williams-Beuren syndrome (WBS). These were detected by fluorescent in situ hybridization (FISH) analysis with specific probes and were excluded from the final analysis. Chromosomal microarray analysis (CMA; single-nucleotide polymorphism-based array-comparative genomic hybridization) was performed as per the clinical indication in selected patients with dysmorphism, microcephaly, mental retardation, and/or multiple malformations. These patients had a negative result on FISH analysis. RESULTS: In suspected patients with PWS, FISH and methylation testing confirmed six cases to be really PWS. FISH also detected five cases of DGS and one case of WBS. These were excluded from the final analysis. Among the 18 cases tested by CMA, in 13 patients, abnormalities with potential clinical significance were identified. Genetic counseling was done in all these cases. Prenatal diagnosis was done in one family. CONCLUSION: In cases with dysmorphism with or without mental retardation or cardiac defect, advanced studies such as CMA can lead to a definitive diagnosis. Genetic counseling is mandatory in all these cases and a prenatal diagnosis is also feasible in selected families.

Differing autonomic responses to dobutamine stress in the presence and absence of myocardial ischaemia.

KEY POINTS: Dobutamine stress echocardiography is a validated tool for the non-invasive evaluation of myocardial ischaemia and enables the recording of heart rate variability in non-resting conditions. In this study we determined whether individuals with transient myocardial ischaemia had different autonomic responses to the stress of dobutamine infusion compared to non-ischaemic (normal) responders. Non-ischaemic responders had a residual predominance of parasympathetic over sympathetic activity. However, under conditions of myocardial ischaemia, there was a directionally opposite cardiac autonomic response with a residual increase of sympathetic over parasympathetic modulation. The sympathetic response to dobutamine stress is augmented as the burden of myocardial ischaemia is increased. ABSTRACT: Cardiac autonomic dysfunction has prognostic significance in patients with coronary artery disease. This investigation aimed to assess changes in autonomic modulation induced by dobutamine stress in the presence and absence of myocardial ischaemia. In total, 314 individuals underwent dobutamine stress echocardiography to detect or exclude myocardial ischaemia. Simultaneous autonomic and haemodynamic data were obtained using a plethysmographic device. Total power spectral density and associated low-frequency (LF) and high-frequency (HF) power spectral components in absolute (ms(2) ) and normalised units (nu) were determined. Participants were categorised as non-ischaemic (NI) or ischaemic (IS) responders. There were no significant differences in LFnu or HFnu between groups at baseline. At peak stress, LFnu decreased from baseline in NI (43 ± 1.8 to 40 ± 1.8%), but increased from baseline in IS responders (39.5 ± 2 to 56 ± 2%, P < 0.05). In contrast, HFnu increased in NI patients (57 ± 1.8 to 60 ± 1.8%) but decreased in IS responders (60.5 ± 2 to 44 ± 2%, P < 0.05). Those with a high ischaemic burden [more than three ischaemic left ventricular (LV) segments] had a greater increase in LFnu (41 ± 4.8 to 65 ± 3.2% vs. 44.8 ± 3.8 to 57.7 ± 3.1%, P < 0.05) and greater decrease in HFnu (59 ± 4.8 to 35 ± 3.2% vs. 55.2 ± 3.8 to 42.3 ± 3.1%, P < 0.05) compared to patients with a low ischaemic burden (1-3 ischaemic LV segments) respectively, at peak stress. In the absence of myocardial ischaemia, dobutamine stress is associated with a residual predominance of parasympathetic over sympathetic activity. Under conditions of ischaemia, there is a directionally opposite autonomic response with a significant residual increase of sympathetic over parasympathetic modulation. This response is augmented as the burden of ischaemia is increased.

The distribution and prognosis of anomalous coronary arteries identified by cardiovascular magnetic resonance: 15 year experience from two tertiary centres.

BACKGROUND: Aberrant coronary arteries represent a diverse group of congenital disorders. Post-mortem studies reveal a high risk of exercise-related sudden cardiac death in those with an anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS) with an inter-arterial course. There is little documentation of lifetime history and long-term follow-up of patients with coronary artery anomalies. METHODS: Patients with anomalous coronary arteries undergoing cardiovascular magnetic resonance over a 15-year period were identified and classified by anatomy and course. Medical records were reviewed for major adverse cardiovascular events (MACE). Revascularisation or myocardial infarction counted only if occurring in the distribution of the anomalous artery. RESULTS: Consecutive patients with coronary artery anomalies were retrospectively identified (n = 172). Median follow-up time was 4.3 years (IQR 2.5-7.8, maximum 15.6). 116 patients had ACAOS of which 64 (55%) had an inter-arterial course (IAC) and 52 (45%) did not. During follow up 110 ACAOS patients were alive, 5 died and 1 lost to follow-up.ACAOS patients experienced 58 MACE events (5 cardiovascular deaths, 5 PCI, 24 CABG and 24 had myocardial infarction). 47 MACE events occurred in ACAOS with IAC and 11 in those without (p < 0.0001), the statistical difference driven by surgical revascularisation and myocardial infarction. CONCLUSIONS: In life, patients with an anomalous coronary artery originating from the opposite sinus of Valsalva taking an IAC have higher rates of both myocardial infarction and surgical revascularisation during long-term follow up, compared to those without IAC.

Appearance of microvascular obstruction on high resolution first-pass perfusion, early and late gadolinium enhancement CMR in patients with acute myocardial infarction.

BACKGROUND: The presence and extent of microvascular obstruction (MO) after acute myocardial infarction can be measured by first-pass gadolinium-enhanced perfusion cardiovascular magnetic resonance (CMR) or after gadolinium injection with early or late enhancement (EGE/LGE) imaging. The volume of MO measured by these three methods may differ because contrast agent diffusion into the MO reduces its apparent extent over time. Theoretically, first-pass perfusion CMR should be the most accurate method to measure MO, but this technique has been limited by lower spatial resolution than EGE and LGE as well as incomplete cardiac coverage. These limitations of perfusion CMR can be overcome using spatio-temporal undersampling methods. The purpose of this study was to compare the extent of MO by high resolution first-pass k-t SENSE accelerated perfusion, EGE and LGE. METHODS: 34 patients with acute ST elevation myocardial infarction, treated successfully with primary percutaneous coronary intervention (PPCI), underwent CMR within 72 hours of admission. k-t SENSE accelerated first-pass perfusion MR (7 fold acceleration, spatial resolution 1.5 mm x 1.5 mm x 10 mm, 8 slices acquired over 2 RR intervals, 0.1 mmol/kg Gd-DTPA), EGE (14 minutes after injection with a fixed TI of 440 ms) and LGE images (1012 minutes after injection, TI determined by a Look-Locker scout) were acquired. MO volume was determined for each technique by manual planimetry and summation of discs methodology. RESULTS: k-t SENSE first-pass perfusion detected more cases of MO than EGE and LGE (22 vs. 20 vs. 14, respectively). The extent of MO imaged by first-pass perfusion (median mass 4.7 g, IQR 6.7) was greater than by EGE (median mass 2.3 g, IQR 7.1, p = 0.002) and LGE (median mass 0.2 g, IQR 2.4, p = 0.0003). The correlation coefficient between MO mass measured by first-pass perfusion and EGE was 0.91 (p < 0.001). CONCLUSION: The extent of MO following acute myocardial infarction appears larger on high-resolution first-pass perfusion CMR than on EGE and LGE. Given the inevitable time delay between gadolinium administration and acquisition of either EGE or LGE images, high resolution first-pass perfusion imaging may be the most accurate method to quantify MO.

Is sensible use being made of an inpatient Holter monitoring and transthoracic echocardiogram service within acute medicine?

Transthoracic echocardiograms (TTE) and 24-hour Holter recordings are commonly requested investigations for patients presenting with symptoms thought to be due to underlying cardiac pathology. The objective of this study was to audit the use of inpatient TTE and Holter monitors in acute medical patients under the care of physicians other than cardiologists within a tertiary cardiology referral centre. This was accomplished by a retrospective analysis of 4,623 TTE and 3,145 Holters reported by cardiologists between 8 October 1999 and 3 November 2005. The age range for Holter monitoring was 16-104 years, mean 70 (SD 18) years. The age range for TTE was 16-101 years, mean 68 (SD 17) years. Of the Holters performed, 69.1% were within normal limits. Atrial fibrillation/flutter was the commonest arrhythmia, found in 787 patients (25.0%). A total of 99 patients were referred to a cardiologist; 47 of these patients were permanently paced. Of the TTE requests to assess left ventricular function, 44.8% were normal. A cardiac source of embolism was found in 1.8% of requests to assess for this. TTE requests for infective endocarditis confirmed the diagnosis in 4.1% of patients. Holter investigation and TTE were commonly requested investigations; a large proportion of both, however, were within normal limits. This suggests that more consideration is required before making the request for Holter investigation and TTE, as more appropriate investigations may be available.