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- Carrick, Richard T., et al.
(author)
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Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe
- 2024
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In: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645.
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Journal article (peer-reviewed)abstract
- Background and Aims Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC.Methods This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed.Results One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans.Conclusions North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.
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- Ammirati, Enrico, et al.
(author)
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Acute Myocarditis Associated With Desmosomal Gene Variants
- 2022
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In: JACC. Heart failure. - : ELSEVIER SCI LTD. - 2213-1779 .- 2213-1787. ; 10:10, s. 714-727
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Journal article (peer-reviewed)abstract
- BACKGROUND The risk of adverse cardiovascular events in patients with acute myocarditis (AM) and desmosomal gene variants (DGV) remains unknown.OBJECTIVES The purpose of this study was to ascertain the risk of death, ventricular arrhythmias, recurrent myocarditis, and heart failure (main endpoint) in patients with AM and pathogenic or likely pathogenetic DGV.METHODS In a retrospective international study from 23 hospitals, 97 patients were included: 36 with AM and DGV (DGV[+]), 25 with AM and negative gene testing (DGV[-]), and 36 with AM without genetics testing. All patients had troponin elevation plus findings consistent with AM on histology or at cardiac magnetic resonance (CMR). In 86 patients, CMR changes in function and structure were re-assessed at follow-up.RESULTS In the DGV(+) AM group (88.9% DSP variants), median age was 24 years, 91.7% presented with chest pain, and median left ventricular ejection fraction (LVEF) was 56% on CMR (P = NS vs the other 2 groups). Kaplan-Meier curves demonstrated a higher risk of the main endpoint in DGV(+) AM compared with DGV(-) and without genetics testing patients (62.3% vs 17.5% vs 5.3% at 5 years, respectively; P < 0.0001), driven by myocarditis recurrence and ventricular arrhythmias. At follow-up CMR, a higher number of late gadolinium enhanced segments was found in DGV(+) AM. CONCLUSIONS Patients with AM and evidence of DGV have a higher incidence of adverse cardiovascular events compared with patients with AM without DGV. Further prospective studies are needed to ascertain if genetic testing might improve risk stratification of patients with AM who are considered at low risk. (J Am Coll Cardiol HF 2022;10:714-727) (c) 2022 by the American College of Cardiology Foundation.
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- Lahrouchi, Najim, et al.
(author)
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Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
- 2020
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In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 142:4, s. 324-338
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Journal article (peer-reviewed)abstract
- Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
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5. |
- Lu, Lei, et al.
(author)
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Comments on "Comments on "A General Theory of Phase Noise in Electrical Oscillators""
- 2008
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In: IEEE Journal of Solid-State Circuits. - 0018-9200. ; 43:9, s. 2170-2170
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Journal article (peer-reviewed)abstract
- A recently published correction to the expression of phase noise in general electrical oscillators, derived through a frequency-domain analysis, is incorrect. We show that the correct conclusion about phase noise is the original one.
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- Mazzanti, Andrea, et al.
(author)
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A 1.4mW 4.90-to-5.65GHz Class-C CMOS VCO with an Average FoM of 194.5dBc/Hz
- 2008
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In: 2008 IEEE International Solid-State Circuits Conference (ISSCC), Digest of Technical Papers. ; , s. 474-629
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Conference paper (peer-reviewed)abstract
- A class-C CMOS harmonic VCO maximizes the oscillation amplitude by operating the active devices operating in class C, while the bias-current noise is naturally rejected by the topology. Drawing 1.4mA from a 1V supply, the 0.13µm CMOS prototype exhibits an average phase noise of -130dBc/Hz at 3MHz offset over the 4.90-to-5.65GHz tuning range, for an FoM of 194.5dBc/Hz.
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7. |
- Mazzanti, Andrea, et al.
(author)
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A Push-Pull Class-C CMOS VCO
- 2013
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In: IEEE Journal of Solid-State Circuits. - 0018-9200. ; 48:3, s. 724-732
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Journal article (peer-reviewed)abstract
- A CMOS oscillator employing differential transistor pairs working in Class-C in push-pull configuration is presented. The oscillator exhibits the same advantages enjoyed by complementary topologies on oscillators based on a single differential pair, while yielding a substantial power consumption reduction thanks to the Class-C operation. The phase-noise performance and the fundamental conditions required to keep the transistors working in Class-C are analyzed in detail. It is shown that, for an optimal performance, both nMOS and pMOS transistors should not be pushed into the deep triode region by the instantaneous resonator voltage, and a simple circuit solution is proposed to accommodate a large oscillation swing. A 0.18-mu m CMOS prototype of the (voltage-controlled) oscillator displays an oscillation frequency from 6.09 to 7.50 GHz. The phase noise at 2-MHz offset is below -120 dBc/Hz with a power dissipation of 2.2 mW, for a state-of-the-art figure-of-merit ranging from 189 to 191 dBc/Hz.
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8. |
- Mazzanti, Andrea, et al.
(author)
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A time-variant analysis of fundamental 1/f3 phase noise in CMOS parallel LC-tank quadrature oscillators
- 2009
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In: IEEE Transactions on Circuits and Systems Part 1: Regular Papers. - 1549-8328. ; 56:10, s. 2173-2180
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Journal article (peer-reviewed)abstract
- This paper presents a rigorous time-variant analysis of the 1/f MOS device noise upconversion into 1/f^3 phase noise for two of the most popular parallel-coupled quadrature CMOS harmonic oscillators. Simple closed-form equations for the fundamental 1/f^3 phase-noise spectrum are derived and validated through SpectreRF simulations, proving that the two topologies display remarkably different sensitivities to the low-frequency noise sources. Based on the developed analysis, useful general design insights are also presented.
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9. |
- Mazzanti, Andrea, et al.
(author)
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Analysis and design of a double-quadrature CMOS VCO for subharmonic mixing at Ka-band
- 2008
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In: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480. ; 56:2, s. 355-363
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Journal article (peer-reviewed)abstract
- In this paper, we analyze the potentials of a four-phase 14-GHz CMOS voltage-controlled oscillator, tailored to a sub-harmonic receiver, for signal processing at Ka-band. When mild phase accuracies between in-phase and quadrature down-converted signals are required, the four-phase oscillator displays roughly the same phase noise figure-of-merit as quadrature oscillator counterparts. However, the operation at half-frequency leads to an improved performance due to a higher quality factor of the tuning varactors, and because the local oscillator circuitry and signal path run at different frequencies, relaxing coupling issues. A detailed time-variant analysis of phase noise in multiphase oscillators is introduced and validated by both simulations and experiments. Prototypes realized in a 65-nm technology occupy an active area of 0.5 mm2 and show the following performances: a 26% frequency tuning range (from 12.2 to 15.9 GHz), maximum phase error from pi/4 of 2deg, and a phase noise of -110 dBc/Hz at 1 MHz from 14 GHz, while consuming 18 mA from 0.8-V supply.
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10. |
- Mazzanti, Andrea, et al.
(author)
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Class-C Harmonic CMOS VCOs, With a General Result on Phase Noise
- 2008
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In: IEEE Journal of Solid-State Circuits. - 0018-9200. ; 43:12, s. 2716-2729
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Journal article (peer-reviewed)abstract
- A harmonic oscillator topology displaying an improved phase noise performance is introduced in this paper. Exploiting the advantages yielded by operating the core transistors in class-C, a theoretical 3.9 dB phase noise improvement compared to the standard differential-pair LC-tank oscillator is achieved for the same current consumption. Further benefits derive from the natural rejection of the tail bias current noise, and from the absence of parasitic nodes sensitive to stray capacitances. Closed-form phase-noise equations obtained from a rigorous time-variant circuit analysis are presented, as well as a time-variant study of the stability of the oscillation amplitude, resulting in simple guidelines for a reliable design. Furthermore, the analysis of phase noise is extended to encompass a general harmonic oscillator, showing that all phase noise relations previously obtained for specific LC oscillator topologies are special cases of a very general and remarkably simple result. Two prototypes of the (voltage-controlled) oscillator are implemented in a standard RF 0.13 m CMOS technology. They are tunable over the frequency bands 4.90-5.65 GHz and 4.50–5.00 GHz, respectively, and display an average phase noise lower than 130 dBc/Hz @ 3 MHz from the carrier with a power consumption of 1.4 mW, for a state-of-the-art figure-of-merit ranging from 193.5 dBc/Hz to 196.0 dBc/Hz.
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