Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Alcohol septal ablation in a pregnant patient with symptomatic hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous disease with common findings of ventricular hypertrophy and diastolic dysfunction. Sometimes the condition can lead to catastrophic cardiac events. Pregnancy poses a larger challenge, given medication restrictions and increased mortality compared to the general population. Case: A 43-year-old pregnant female with a history of HCM was referred to cardiology after a murmur was heard at her 12 week gestational appointment. Her exam revealed a grade III/VI systolic ejection murmur that increased in intensity with Valsalva. Her transthoracic echocardiogram (TTE) revealed a resting left ventricular outflow tract (LVOT) obstruction with a gradient of 70mmHg at rest. TTE was also notable for a thick basal septum, systolic anterior motion of the mitral valve and hyperdynamic left ventricular function. She had only minimal shortness of breath and no episodes of lightheadedness. She was next seen at 25 weeks of gestation, and noted progression of symptoms, including shortness of breath with minimal activity and some episodes of lightheadedness despite being on a high dose beta blocker with heart rates in the 60s. A repeat TTE at this time showed an increase in the LVOT obstruction gradient to 90 mmHg. Decision Making: The patient was started on Norpace with initial hospital observation. Unfortunately, the patient’s symptoms persisted and Norpace titration was limited due to a prolonged QTc. Given this, we proceeded with alcohol septal ablation. The procedure was successful without complication. Post-procedure, she had significant runs of symptomatic nonsustained ventricular tachycardia and received an implantable cardiac defibrillator prior to discharge. At her 1 month follow-up, her TTE showed no resting or provoked LVOT gradient and she was asymptomatic. Delivery was uncomplicated at week 37. Norpace was discontinued after delivery and patient has been maintained on beta blockade without symptoms post pregnancy. Conclusions: This case shows a detailed approach to the management of a pregnant patient with HCM. If medical therapy fails, successful alcohol septal ablation can improve the LVOT gradient and relieve symptoms

Excellence and durability: A normally functioning Björk-Shiley flat-disc prosthesis 42 years post implantation

Mechanical heart valves have been used worldwide for more than 60 years. While the composition and design of the valves, and the surgical techniques employed to implant them, have changed and advanced over that time, some of the earlier mechanical heart valves showed such great durability that they are still functioning in patients today. One of the most often-used and long-lasting mechanical prostheses was the Björk-Shiley heart valve. While many versions of this valve were used during its 25 years of production, the most durable was the Björk-Shiley flat-disc valve. This valve was first implanted in 1971 and was the first successful tilting-disc valve. Here, the complex medical history is reported of an elderly patient with a well-functioning Björk-Shiley flat-disc valve in the aortic position that was placed over 42 years ago. The history of mechanical heart valves - in particular the Björk-Shiley heart valve, including the flat-disc mechanical valve - is also briefly reviewed

Valvuloplasty in woman with heterotaxy syndrome

BACKGROUND: Anatomic variations can make structural interventions challenging and require a more creative approach. Persistent left superior vena cava is an uncommon entity; even more uncommon is a left-sided inferior vena cava connecting to the persistent superior vena cava with eventual drainage to the coronary sinus. Heterotaxia is another twist on normal anatomy, and rarer still. CASE: A 77-year-old woman with chronic atrial fibrillation and New York Heart Association (NYHA) functional class III heart failure symptoms requiring supplemental oxygen underwent transthoracic echocardiography and was noted to have severe rheumatic mitral stenosis (resting mean gradient of 10 mmHg, valve area \u3c1 cm2 ), severe pulmonary hypertension and a severely dilated left atrium. Left heart catheterization showed no significant coronary artery disease. Right heart catheterization via a right femoral approach delineated a left-sided inferior vena cava that drained into a left-sided superior vena cava with drainage into the coronary sinus. Computed tomography showed heterotaxy syndrome: polysplenia, midline liver, right-sided stomach and left-sided inferior vena cava. Given her severe, symptomatic mitral stenosis, balloon valvuloplasty was needed. DECISION‐MAKING: Traditionally, mitral balloon valvuloplasty is performed via a transseptal approach. Given her uncharacteristic vascular anatomy, this was deemed high risk. Prior accounts of mitral interventions via a transapical approach have been described, and this approach was deemed a safer method in this case. Therefore, under transesophageal and fluoroscopic guidance, she underwent mitral valvuloplasty via a transapical route. Multiple balloon inflations were performed successfully; her postprocedure gradient was only 5 mmHg, her heart failure symptoms improved to NYHA class I, and she was weaned from supplemental oxygen. CONCLUSIONS: This case illustrates unconventional anatomical variations, rarely encountered as individual entities, let alone in the same patient. Structural interventions, as described in this case, can still be safely undertaken with careful planning and consideration for alternative approaches

Use of Coronary Techniques in Celiac and Hepatic Artery Stenting in Post-Hepatic Transplant Patients

Hepatic artery stenosis (HAS) remains a rare but serious complication after liver transplantation. While invasive surgical techniques were needed for HAS treatment in the past, recently endovascular techniques, including hepatic artery stenting, have been proven to be a safe and effective treatment. The present work focused on a review of the recent literature regarding HAS as well as recent cases demonstrating the various presentations of HAS and the variety of approaches to endovascular intervention. Our single-center experience has shown endovascular treatment of HAS to be safe and effective, including the two specific cases discussed here. While further research is needed, endovascular stenting as a treatment for HAS appears to be a promising, minimally invasive technique to help aid in the long-term health of post-liver transplant patients

Use of Coronary Techniques in Celiac and Hepatic Artery Stenting in Post-Hepatic Transplant Patients

Hepatic artery stenosis (HAS) remains a rare but serious complication after liver transplantation. While invasive surgical techniques were needed for HAS treatment in the past, recently endovascular techniques, including hepatic artery stenting, have been proven to be a safe and effective treatment. The present work focused on a review of the recent literature regarding HAS as well as recent cases demonstrating the various presentations of HAS and the variety of approaches to endovascular intervention. Our single-center experience has shown endovascular treatment of HAS to be safe and effective, including the two specific cases discussed here. While further research is needed, endovascular stenting as a treatment for HAS appears to be a promising, minimally invasive technique to help aid in the long-term health of post-liver transplant patients

Use of Coronary Techniques in Celiac and Hepatic Artery Stenting in Post-Hepatic Transplant Patients

Hepatic artery stenosis (HAS) remains a rare but serious complication after liver transplantation. While invasive surgical techniques were needed for HAS treatment in the past, recently endovascular techniques, including hepatic artery stenting, have been proven to be a safe and effective treatment. The present work focused on a review of the recent literature regarding HAS as well as recent cases demonstrating the various presentations of HAS and the variety of approaches to endovascular intervention. Our single-center experience has shown endovascular treatment of HAS to be safe and effective, including the two specific cases discussed here. While further research is needed, endovascular stenting as a treatment for HAS appears to be a promising, minimally invasive technique to help aid in the long-term health of post-liver transplant patients

Patients with hypertensive responses to exercise or dobutamine stress testing differ in resting hypertensive phenotype

Little is known of the importance of echocardiographic measures of resting systemic vascular resistance (SVR), cardiac output, and diastolic function in the development of a hypertensive response during dobutamine stress echocardiography. We performed a retrospective review of 325 subjects who underwent stress echocardiography and a resting echocardiogram on the same day. Logistical regressions were performed to determine associations between hypertensive response to each type of stress test and clinical and hemodynamic measurements obtained by transthoracic echocardiography. Patients with a hypertensive response to dobutamine or exercise stress modalities had Stage 1 hypertension. Those with a hypertensive response to dobutamine had a significantly elevated SVR and a lower cardiac output compared to those with a hypertensive response to exercise or a nonhypertensive response to dobutamine. An SVR ≥2000 dynes × sec/c