The physician should be alert to the possibility of cardiac disease in SSc; it is best managed within a multidisciplinary team including both rheumatologists and cardiologists. This pathway provides a reference for all physicians managing patients with SSc.

MVA planimetry is feasible in the majority of patients with RhMS using 3DTEE, with excellent reproducibility, and compares favorably with established methods. Three-dimensional transesophageal echocardiography allows excellent assessment of commissural fusion.

Key PointsQuestionIs transcatheter aortic valve implantation (TAVI) noninferior to surgical aortic valve replacement (surgery) in patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk?FindingsIn this randomized clinical trial that included 913 patients at moderately increased operative risk due to age or comorbidity, all-cause mortality at 1 year was 4.6% with TAVI vs 6.6% with surgery, a difference that met the prespecified noninferiority margin of 5%.MeaningAmong patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, treatment with TAVI was noninferior to surgery with respect to all-cause mortality at 1 year.

ImportanceIn patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited.ObjectiveTo report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial.Design, Setting, and ParticipantsSURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021.InterventionPatients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis.Main Outcomes and MeasuresThe prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years.ResultsA total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention.Conclusions and RelevanceAmong intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

Background: While information on how cardiac resynchronisation therapy (CRT) affects cardiac performance at rest is readily available, the mechanisms whereby CRT alters cardiac function during maximal exercise are unclear. Aims: We examined the medium-term effects of CRT on cardiac and physical functional reserve of patients with severe heart failure (CHF) and prolonged QRS duration. Methods: Seventeen consecutive patients with severe CHF (NYHA III -IV) and widened QRS underwent maximal cardiopulmonary exercise testing with non-invasive central haemodynamic measurements before and 6 -8 weeks after CRT pacemaker implantation. Results: After CRT there were significant increases in exercise cardiac output by 19.3% ( P = 0.0048) from 9.5 T 3.4 l min À 1 , peak mean arterial blood pressure by 14.1% ( P = 0.0001) from 91.3 T 13.6 mm Hg, and peak cardiac power output by 37.2% ( P = 0.0008) from 1.92 T 0.74 W. There were no significant changes in these variables at rest. Exercise duration (+ 42.3%, P = 0.0002), NYHA functional class ( P = 0.0001) and SF-36 symptom score ( P = 0.0006) were also significantly improved. Powerful surrogate indicators of prognosis were also significantly improved with CRT: peak O 2 consumption (+20.9%, P = 0.0007), VE/VCO 2 slope (À 20.0%, P = 0.005) and circulatory power (+ 42.0%, P = 0.0012). Conclusion: In this cohort of patients, post-implant CRT significantly improved the flow-, pressure-and power-generating capacity of the failing hearts. This may be causally related to the improvements observed in exercise capacity, functional class and symptom scores.

The natural history of mitral regurgitation (MR) results in significant morbidity and mortality. Innovations in non-invasive imaging have provided new insights into the pathophysiology and quantification of MR, in addition to early detection of left ventricular (LV) dysfunction and prognostic assessment in asymptomatic patients. Transthoracic (TTE) and transesophageal (TOE) echocardiography are the mainstay for diagnosis, assessment and serial surveillance. However, the advance from 2D to 3D imaging leads to improved assessment and characterization of mitral valve (MV) disease. Cardiovascular magnetic resonance (CMR) is increasingly used for MR quantitation and can provide an alternative imaging method if echocardiography is suboptimal or inconclusive. Other techniques such as exercise echocardiography, tissue Doppler imaging and speckle-tracking echocardiography can further offer complementary information on prognosis. This review summarises the current evidence for state-of-the-art cardiovascular imaging for the investigation of MR. Whilst advanced echocardiographic techniques are superior in the evaluation of complex MV anatomy, CMR appears the most accurate technique for the quantification of MR severity. Integration of multimodality imaging for the assessment of MR utilises the advantages of each imaging technique and offers the most comprehensive assessment of MR.

To investigate the mechanisms of transcriptional activation of interleukin-1beta (IL-1beta) in non-monocytic cells, we constructed a series of reporter plasmids with the bacterial chloramphenicol acetyltransferase gene linked to various parts of the human IL-1beta promoter and performed transient transfection experiments. We identified a promoter segment that activates transcription most efficiently in keratinocytes. Electrophoretic mobility shift assays (EMSA) with a 43-mer oligonucleotide derived from the functionally identified cis-acting element revealed specific complexes. By competition analysis with transcription factor consensus sequence oligonucleotides and by immunosupershift, transcription factor SP-1 or a closely related protein was shown to bind to this regulatory element. The closest match to the known SP-1 consensus sequence within the respective region is a TCCCCTCCCCT motif. Mutation of this motif almost completely, and specifically, abolished the binding of two low-mobility complexes and led to a 95% decrease of constitutive transcriptional activation of a reporter construct IL-1beta (-170/+108). Likewise, activation of this reporter construct by tumor necrosis factor-alpha depended on the SP-1 site. These observations suggest that a so-far-unrecognized SP-1 site in the human IL-1beta promoter may participate in the transcriptional regulation of this gene in keratinocytes.

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