Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature – The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11)

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code ( IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC. The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature. The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature – The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11)

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Coupling between Blood Pressure and Subarachnoid Space Width Oscillations during Slow Breathing

The precise mechanisms connecting the cardiovascular system and the cerebrospinal fluid (CSF) are not well understood in detail. This paper investigates the couplings between the cardiac and respiratory components, as extracted from blood pressure (BP) signals and oscillations of the subarachnoid space width (SAS), collected during slow ventilation and ventilation against inspiration resistance. The experiment was performed on a group of 20 healthy volunteers (12 females and 8 males; BMI =22.1±3.2 kg/m2; age 25.3±7.9 years). We analysed the recorded signals with a wavelet transform. For the first time, a method based on dynamical Bayesian inference was used to detect the effective phase connectivity and the underlying coupling functions between the SAS and BP signals. There are several new findings. Slow breathing with or without resistance increases the strength of the coupling between the respiratory and cardiac components of both measured signals. We also observed increases in the strength of the coupling between the respiratory component of the BP and the cardiac component of the SAS and vice versa. Slow breathing synchronises the SAS oscillations, between the brain hemispheres. It also diminishes the similarity of the coupling between all analysed pairs of oscillators, while inspiratory resistance partially reverses this phenomenon. BP–SAS and SAS–BP interactions may reflect changes in the overall biomechanical characteristics of the brain.

The mechanisms behind perivascular fluid flow

Flow of cerebrospinal fluid (CSF) in perivascular spaces (PVS) is one of the key concepts involved in theories concerning clearance from the brain. Experimental studies have demonstrated both net and oscillatory movement of microspheres in PVS (Mestre et al. (2018), Bedussi et al. (2018)). The oscillatory particle movement has a clear cardiac component, while the mechanisms involved in net movement remain disputed. Using computational fluid dynamics, we computed the CSF velocity and pressure in a PVS surrounding a cerebral artery subject to different forces, representing arterial wall expansion, systemic CSF pressure changes and rigid motions of the artery. The arterial wall expansion generated velocity amplitudes of 60–260 μm/s, which is in the upper range of previously observed values. In the absence of a static pressure gradient, predicted net flow velocities were small (<0.5 μm/s), though reaching up to 7 μm/s for non-physiological PVS lengths. In realistic geometries, a static systemic pressure increase of physiologically plausible magnitude was sufficient to induce net flow velocities of 20–30 μm/s. Moreover, rigid motions of the artery added to the complexity of flow patterns in the PVS. Our study demonstrates that the combination of arterial wall expansion, rigid motions and a static CSF pressure gradient generates net and oscillatory PVS flow, quantitatively comparable with experimental findings. The static CSF pressure gradient required for net flow is small, suggesting that its origin is yet to be determined.

Cardiac and Pulmonary Safety Profile of Single-Agent Carfilzomib From Four Phase 2 Studies in Patients with Relapsed and/or Refractory Multiple Myeloma

Abstract 4037 Background: Cardiac and pulmonary events are common comorbidities in patients (pts) with multiple myeloma (MM) that typically affect older adults (Robin J, et al. J Med Case Rep. 2008) and are aggravated by chronic anemia and cardiotoxicity of anti-MM agents such as anthracyclines and hematopoietic stem cell transplantation (Chow AW, et al. Intern Med J. 2012). Pts with MM are also predisposed to pulmonary infections, with pneumonia being one of the most common causes of death (Augustson BM, et al. J Clin Oncol.2005). The following abstract summarizes details of the cardiac and pulmonary safety profile from 4 phase 2 studies of carfilzomib (CFZ), a next generation proteasome inhibitor recently approved for the treatment of relapsed and refractory MM. Methods: Included in this analysis were 526 pts with relapsed and/or refractory MM treated with CFZ in the following trials: 003-A0, 003-A1, 004, and 005. In all studies, CFZ was dosed on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle (C). Doses could be escalated from 20 mg/m2 in C1 to 27 mg/m2 in C2 for all studies except 005 (15 mg/m2 in C1, 20 mg/m2 in C2, and 27 mg/m2in C3). Pts with NYHA class III-IV heart failure and recent MI/unstable angina were excluded. A comprehensive strategy based on Standardized MedDRA Query preferred terms was used wherein clinically related event terms were grouped to determine the most comprehensive occurrences of adverse events (AEs). The cardiac grouping included cardiac arrhythmias, cardiac failure, cardiomyopathy, and ischemic heart disease (IHD). Medical history was analyzed for relevant comorbid conditions, and baseline cardiac risk factor was defined as pts on ≥1 prior cardiac medication. Multiple dyspnea AE terms were grouped as were pulmonary infections from the Infections and Infestations System Organ Classes. Pulmonary AE analyses included dyspnea time-to-event and duration-of-event analyses. Results: In all, 73.6% pts had a medical history of a cardiac event and 70.0% demonstrated baseline cardiac risk factors. The most common cardiac AEs were arrhythmias, the majority of which were low-grade, benign, supra-ventricular events such as tachycardia and palpitations. Congestive heart failure (CHF) events were predominantly Grade (G) 3. There were 4 (0.8%) G5 cardiac SAEs, all cardiac arrest. An additional 4 pts had a cardiac component to their death for a total of 8 (1.5%) deaths on study or within 30 days of treatment with a cardiac component. Of note, 7 of the 8 deaths occurred in pts with baseline cardiac risk factors. Overall, 6 pts (1.1%) had a CFZ dose reduction and 23 (4.4%) discontinued treatment due to a cardiac AE. Cardiac events leading to discontinuation included CHF (1.7%), arrhythmia (1.1%), and IHD (1.0%). In general, the rate of cardiac events decreased over time with increased of number of cycles (C1 52/526 pts, 9.9%; C9–11 3/154 pts, 1.9%). The most commonly reported pulmonary AE was dyspnea (42.2%). Of note, the majority of the dyspnea events were G1 or G2 with 1 G5 dyspnea occurring in the clinical setting of CHF. Dyspnea was reported by a higher percentage of pts in earlier cycles vs later cycles (11.8% in C1; 3.2% in C6), suggesting it is likely not associated with cumulative toxicity. The median duration of a dyspnea event was 8 days and the majority of episodes were transient, with 64% lasting <2 weeks. Notably, no interstitial lung disease (ILD) or pulmonary fibrosis AEs were reported. At least 1 pulmonary infection AE was reported for 18.8% of pts; pneumonia was the most common AE (67 pts, 12.7%) as well as the most common SAE (52 pts, 9.9%). Pulmonary infections resulted in the death of 2 pts. Conclusion: Cardiac event deaths and deaths with a cardiac etiology are not unexpected in this heavily pretreated, late-stage population. Rates reported here are comparable to those noted in the literature for this population. While dyspnea was frequently observed, events were mainly G1 or G2 and transient, and there were no AEs of ILD or pulmonary fibrosis. Pulmonary infection rates were comparable to those previously reported in the literature. Importantly, CFZ discontinuations and dose reductions due to these AEs were uncommon. Cardiac and pulmonary AEs are being further characterized in ongoing randomized clinical trials. Disclosures: Lonial: Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Onyx Pharmaceuticals: Consultancy; Merck: Consultancy. Off Label Use: Carfilzomib for the treatment of Multiple Myeloma. Niesvizky:Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau; Onyx Pharmaceuticals: Consultancy, Research Funding. McCulloch:Onyx Pharmaceuticals: Employment. Rajangam:Onyx Pharmaceuticals: Employment. Vij:Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium: Speakers Bureau; Onyx Pharmaceuticals: Consultancy, Research Funding.