Medicine 2032: The future of cardiovascular disease prevention with machine learning and digital health technology.

Machine learning (ML) refers to computational algorithms that iteratively improve their ability to recognize patterns in data. The digitization of our healthcare infrastructure is generating an abundance of data from electronic health records, imaging, wearables, and sensors that can be analyzed by ML algorithms to generate personalized risk assessments and promote guideline-directed medical management. ML's strength in generating insights from complex medical data to guide clinical decisions must be balanced with the potential to adversely affect patient privacy, safety, health equity, and clinical interpretability. This review provides a primer on key advances in ML for cardiovascular disease prevention and how they may impact clinical practice.

Infant Nutrition in Low- and Middle-Income Countries.

The burden of infant malnutrition is greatest in low- and middle-income countries (LMICs). Infant malnutrition is defined based on distinct subcategories, among them stunting (low-height-for-age) and wasting (low-weight-for-height). Some experts are shifting more toward understanding the interplay between these overlapping phenotypes and other confounding factors such as maternal nutrition and environmental hygiene. Current guidelines emphasize appropriate breastfeeding and nutrition within the 1000 days from conception to a child's second birthday to optimize early development. Future research directed toward better biomarkers of malnutrition before acute clinical symptoms develop will help direct targeted efforts toward at-risk populations.

Distribution of Coronary Artery Calcium by Age, Sex, and Race Among Patients 30-45 Years Old.

BACKGROUND: Coronary artery calcium (CAC) is a measure of atherosclerotic burden and is well-validated for risk stratification in middle- to older-aged adults. Few studies have investigated CAC in younger adults, and there is no calculator for determining age-, sex-, and race-based percentiles among individuals aged <45 years. OBJECTIVES: The purpose of this study was to determine the probability of CAC >0 and develop age-sex-race percentiles for U.S. adults aged 30-45 years. METHODS: We harmonized 3 datasets-CARDIA (Coronary Artery Risk Development in Young Adults), the CAC Consortium, and the Walter Reed Cohort-to study CAC in 19,725 asymptomatic Black and White individuals aged 30-45 years without known atherosclerotic cardiovascular disease. After weighting each cohort equally, the probability of CAC >0 and age-sex-race percentiles of CAC distributions were estimated using nonparametric techniques. RESULTS: The prevalence of CAC >0 was 26% among White males, 16% among Black males, 10% among White females, and 7% among Black females. CAC >0 automatically placed all females at >90th percentile. CAC >0 placed White males at the 90th percentile at age 34 years compared with Black males at age 37 years. An interactive webpage allows one to enter an age, sex, race, and CAC score to obtain the corresponding estimated percentile. CONCLUSIONS: In a large cohort of U.S. adults aged 30-45 years without symptomatic atherosclerotic cardiovascular disease, the probability of CAC >0 varied by age, sex, and race. Estimated percentiles may help interpretation of CAC scores among young adults relative to their age-sex-race matched peers and can henceforth be included in CAC score reporting.

Spontaneous Multivessel Coronary Spasm During Diagnostic Coronary Angiography.

Acute vasospastic angina, formerly known as Prinzmetal angina, is characterized by transient electrocardiographic changes that are not related to exertion. Its atypical presentation makes it difficult to establish the diagnosis, so it is probably underrecognized and therefore mismanaged. We treated a 49-year-old woman who presented with a 2-day history of chest pain associated with palpitations. Abnormal radionuclide stress test results prompted diagnostic coronary angiography, during which the patient reported chest pain and became hemodynamically unstable. Active coronary vasospasm at multiple sites was treated with intracoronary nitroglycerin and nicardipine, leading to immediate recovery. Our case highlights the importance of accurate, timely diagnosis of vasospastic angina, and of early recognition and management of spontaneous coronary spasm during angiography.

Can Milking-Like Effect Be the First Clue of a Ventricular Free Wall Rupture?

Ventricular free wall rupture (VFWR) is a catastrophic complication of myocardial infarction that poses an imminent surgical emergency. Early recognition is essential as it can expedite the process for a life-saving surgical intervention. We present a case of an acute left VFWR resulting from an underlying myocardial infarction which showed a "milking-like effect" during diagnostic angiography. "Milking-like effect" is an angiographic phenomenon typically seen in myocardial bridging, which occurs due to the compression of the intramyocardial coronary segments during systole. The presence of this phenomenon is believed to occur due to the extrinsic compression of the coronary by the evolving hemopericardium.

Machine Learning Predictive Outcomes Modeling in Inflammatory Bowel Diseases.

There is a rising interest in use of big data approaches to personalize treatment of inflammatory bowel diseases (IBDs) and to predict and prevent outcomes such as disease flares and therapeutic nonresponse. Machine learning (ML) provides an avenue to identify and quantify features across vast quantities of data to produce novel insights in disease management. In this review, we cover current approaches in ML-driven predictive outcomes modeling for IBD and relate how advances in other fields of medicine may be applied to improve future IBD predictive models. Numerous studies have incorporated clinical, laboratory, or omics data to predict significant outcomes in IBD, including hospitalizations, outpatient corticosteroid use, biologic response, and refractory disease after colectomy, among others, with considerable health care dollars saved as a result. Encouraging results in other fields of medicine support efforts to use ML image analysis-including analysis of histopathology, endoscopy, and radiology-to further advance outcome predictions in IBD. Though obstacles to clinical implementation include technical barriers, bias within data sets, and incongruence between limited data sets preventing model validation in larger cohorts, ML-predictive analytics have the potential to transform the clinical management of IBD. Future directions include the development of models that synthesize all aforementioned approaches to produce more robust predictive metrics.

Predictors of Coronary Artery Calcium and Long-Term Risks of Death, Myocardial Infarction, and Stroke in Young Adults.

Background Coronary artery calcium (CAC) is well-validated for cardiovascular disease risk stratification in middle to older-aged adults; however, the 2019 American College of Cardiology/American Heart Association guidelines state that more data are needed regarding the performance of CAC in low-risk younger adults. Methods and Results We measured CAC in 13 397 patients aged 30 to 49 years without known cardiovascular disease or malignancy between 1997 and 2009. Outcomes of myocardial infarction (MI), stroke, major adverse cardiovascular events (MACE; MI, stroke, or cardiovascular death), and all-cause mortality were assessed using Cox proportional hazard models, controlling for baseline risk factors (including atrial fibrillation for stroke and MACE) and the competing risk of death or noncardiac death as appropriate. The cohort (74% men, mean age 44 years, and 76% with ≤1 cardiovascular disease risk factor) had a 20.6% prevalence of any CAC. CAC was independently predicted by age, male sex, White race, and cardiovascular disease risk factors. Over a mean of 11 years of follow-up, the relative adjusted subhazard ratio of CAC >0 was 2.9 for MI and 1.6 for MACE. CAC >100 was associated with significantly increased hazards of MI (adjusted subhazard ratio, 5.2), MACE (adjusted subhazard ratio, 3.1), stroke (adjusted subhazard ratio, 1.7), and all-cause mortality (hazard ratio, 2.1). CAC significantly improved the prognostic accuracy of risk factors for MACE, MI, and all-cause mortality by the likelihood ratio test (P<0.05). Conclusions CAC was prevalent in a large sample of low-risk young adults. Those with any CAC had significantly higher long-term hazards of MACE and MI, while severe CAC increased hazards for all outcomes including death. CAC may have utility for clinical decision-making among select young adults.

Maternal and Fetal Outcome of Pregnant Patients Having Preexisting Cardiovascular Disease.

Introduction Cardiovascular disease is common in woman of all age, including child bearing age. In this study, we aim to compare maternal and fetal outcome in pregnant woman with and without preexisting cardiovascular disease. Methods This case control single center study was conducted by Obstetrics & Gynecology department and Cardiology department Shaikh Zayed Medical College/Hospital Rahimyar Khan from 1st March 2020 to 30th June 2020. Results Pregnant woman with preexisting cardiovascular disease had more preterm births and newborn with lower birth weight. Maternal and fetal deaths were numerical higher in pregnant women with preexisting cardiovascular disease but statistically non-significant compared to woman without preexisting cardiovascular disease. Conclusion It is important to identify underlying cardiovascular disease in pregnant woman. Proper counselling throughout pregnancy is needed and efforts should be made to minimize risk of maternal and fetal complications.

Septal ablation acutely reduces outflow obstruction after transcatheter mitral valve replacement.

Transcatheter mitral valve replacement (TMVR) is an emerging treatment of mitral valve pathology in patients that are not candidates for conventional surgical approaches. Higher rates of left ventricular outflow tract obstruction (LVOTO) may occur following TMVR and its occurrence is an independent predictor of mortality. We present a case of severe mitral stenosis and annular calcification that was treated with a balloon-expandable Sapien S3 valve in the mitral position delivered through surgical port-access approach, which resulted in postoperative LVOTO. The LVOTO was successfully treated with alcohol septal ablation with immediate reduction in outflow tract gradients and long-term resolution.

Thyroid Storm-induced Severe Dilated Cardiomyopathy and Ventricular Tachycardia.

Thyroid storm is an extreme form of hyperthyroidism associated with a high mortality rate. Heart failure is considered the leading cause of mortality in patients with thyroid storm, though the underlying cardiac pathology is unclear. Approximately 6% of patients with thyroid storm have heart failure symptoms as the initial presenting complaint. Roughly, one-third of these patients develop dilated cardiomyopathy (DCM). In this report, we present a case of cardiogenic pulmonary edema and sustained ventricular tachycardia in a patient with hyperthyroidism presenting with thyroid storm.

Ineffective Antibiotic Prophylaxis: An Unusual Presentation of Infective Endocarditis with Insights into the Appropriateness of Prophylaxis.

The practice of antibiotic prophylaxis for the prevention of infective endocarditis (IE) has undergone a major paradigm shift over the past few decades. From the earlier practice of antibiotic prophylaxis for all patients undergoing dental procedures, since 2006, the American College of Cardiology/American Heart Association (ACC/AHA) guidelines have now narrowed down the indications to use it only in patients at high risk for IE. A true concern for antibiotic resistance remains eminent when used without appropriate indications. Through this case presentation of IE and the associated preceding use of antibiotics, we take this opportunity to explain the appropriateness of prophylaxis in patients from different risk groups. We also shed some light on alternative, effective, and, yet, harmless measures for the prevention of IE in patients at low risk.

Marijuana-associated ST-elevation myocardial infarction: is this a benign drug.

Marijuana is the most commonly used psychoactive drug in the USA. A 35-year-old man with a medical history of marijuana abuse is admitted to the hospital due to crushing substernal chest pain. ECG shows evolving ST-segment elevation with a rise in cardiac enzymes, consistent with ST-elevation myocardial infarction. A urine toxicology screen is positive for cannabis and negative for cocaine and other stimulant drugs. An emergent cardiac catheterisation reveals no evidence of coronary artery disease or thrombosis. A diagnosis of coronary vasospasm is strongly considered, and the patient is started on calcium channel blocker, with a resolution of symptoms and ECG changes. Marijuana-induced coronary spasm causing myocardial infarction has rarely been reported. Marijuana is becoming a social norm in adolescents and there remains a misconception that it is harmless and even beneficial. Increasing drug abuse remains a public health concern, necessitating population education by physicians for safer healthcare practices.

Reprint of: Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer.

Cancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level without the need for invasively acquired samples from primary or metastatic lesions. This potential for molecular analysis makes ccfDNA attractive for the study of clonal evolution and for uncovering emerging therapeutic resistance or sensitivity. We assessed ccfDNA from colon and pancreatic adenocarcinoma patients using next generation sequencing of 56 cancer-associated genes at the time of primary resectable disease and metastatic progression and compared this to the mutational patterns of the primary tumor. 28%-47% of non-synonymous mutations in the primary tumors were also detected in the ccfDNA while 71%-78% mutations found in ccfDNA were not detected in the primary tumors. ccfDNA collected at the time of progression harbored 3-5 new mutations not detected in ccfDNA at the earlier collection time points. We conclude that incorporation of ccfDNA analysis provides crucial insights into the changing molecular makeup of progressive colon and pancreatic cancer.

Hypoglycemia-associated In-stent Thrombosis: Are We Doing Too Much?

Diabetes mellitus is one of the most common modifiable risk factors for coronary artery disease, and its prevalence is rising globally. Persistent hyperglycemia has a well-established cardiovascular risk, and its treatment plays an important role in the prevention of future cardiovascular events. While we improved microvascular complications such as retinopathy, nephropathy, and neuropathy by stringent blood glucose control, the cardiovascular morbidity and mortality in diabetics remain high. Hypoglycemia, on the other hand, is an important side effect of pharmaceutical blood glucose control, especially those who are treated with insulin. Here, we report the case of a 38-year-old man with type 1 diabetes presenting twice with acute ST-elevation myocardial infarction, both in the setting of documented hypoglycemia. There are reported cases of acute cardiovascular events or silent myocardial ischemia associated with hypoglycemia, and we wish to raise awareness for clinicians who treat this special population of patients.

Circulating cell-free DNA mutation patterns in early and late stage colon and pancreatic cancer.

Cancer is a heterogeneous disease harboring diverse subclonal populations that can be discriminated by their DNA mutations. Environmental pressure selects subclones that ultimately drive disease progression and tumor relapse. Circulating cell-free DNA (ccfDNA) can be used to approximate the mutational makeup of cancer lesions and can serve as a marker for monitoring disease progression at the molecular level without the need for invasively acquired samples from primary or metastatic lesions. This potential for molecular analysis makes ccfDNA attractive for the study of clonal evolution and for uncovering emerging therapeutic resistance or sensitivity. We assessed ccfDNA from colon and pancreatic adenocarcinoma patients using next generation sequencing of 56 cancer-associated genes at the time of primary resectable disease and metastatic progression and compared this to the mutational patterns of the primary tumor. 28%-47% of non-synonymous mutations in the primary tumors were also detected in the ccfDNA while 71%-78% mutations found in ccfDNA were not detected in the primary tumors. ccfDNA collected at the time of progression harbored 3-5 new mutations not detected in ccfDNA at the earlier collection time points. We conclude that incorporation of ccfDNA analysis provides crucial insights into the changing molecular makeup of progressive colon and pancreatic cancer.

Prompt delivery of thrombolytic therapy: experience with chest pain units and emergency medical services.

OBJECTIVE: To reduce the reperfusion time with thrombolytics. METHODS: The study was done at Sheikh Zayed Hospital, Rahimyar Khan, between January and October 2009, and comprised all consecutive patients with ST segment Myocardial Infarction presenting to the hospital in emergency. In phase one, emergency medical services of Rescue 1122 were utilised to minimize transportation time and thrombolytics were instituted in the Emergency Department or the Coronary Care Unit. In Phase II, a chest pain unit was established in the Emergency Department and all patients were thrombolysed there. A proforma describing Total time, Door-to-needle time, demographics, reperfusion criteria, immediate and delayed complications was filled up for each patient. Comparative groups were analysed using Chi-square and Kruskal-Wallis tests, and p < 0.05 was considered statistically significant. RESULTS: A total of 291 patients were enrolled. Of them 15 (5.15%) were rescued by the emergency medical services, while 276 (94.84%) presented themselves or were referred. Mean age was 51 +/- 11.5 years. There were 245 (84%) males. Thirty (10.30%) patients were thrombolysed at the Chest Pain Unit; 216 (74.22%) at the Coronary Care Unit; and 45 (15.46%) in the Emergency Department. Total time was 3:52, 5:29, and 4:55 hours respectively (p = 0.003). Door-to-needle time was significantly reduced in the chest pain unit (p = 0.0001). Total time was minimum in emergency medical services (p = 0.0001). ST segment resolution > 70% was maximum in the chest pain unit (p = 0.0001). CONCLUSION: There was remarkable reduction in Total time utilising emergency medical services and door-to-needle time by establishing the chest pain unit. It is strongly recommended thatsuch units be developed in all districts and tertiary care hospitals as a cost-effective facility.

Outcomes after sirolimus- and paclitaxel-eluting stent implantation in patients with insulin-treated diabetes mellitus.

Insulin-treated diabetic patients undergoing drug-eluting stent implantation are prone to high rates of adverse cardiac events. The efficacy of the sirolimus- (SES) and paclitaxel-eluting stent (PES) in this population was analyzed. Registry data for 434 consecutive patients with insulin-treated diabetes who underwent SES or PES implantation were analyzed. The end point, major adverse cardiac events (MACEs) at 1 year, was high for patients with SESs and PESs (20.6% vs 20.2%; p=0.91). Cox regression and propensity analysis were used to compare outcomes. The adjusted hazard ratio (HR) for MACEs according to stent type (Cox model) was 1.0 (95% confidence interval [CI] 0.64 to 1.76, p=0.82). The propensity score-adjusted (C statistic=0.66) HR was 0.95 (95% CI 0.56 to 1.61, p=0.84). Stent thrombosis rates were relatively high at 2.0% for SESs and 1.5% for PESs (p=0.49). The propensity score-adjusted HR for stent thrombosis was 2.7 (95% CI 0.31 to 23.6, p=0.37). In conclusion, SESs and PESs are similarly efficacious in insulin-treated diabetic patients. The high MACE and stent thrombosis rates are of concern. Additional studies in this group of patients are required to determine the optimal mode of revascularization and minimize the overall stent thrombosis rate.

Adjunct thrombus aspiration reduces mortality in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction with high-risk angiographic characteristics.

Routine aspiration thrombectomy (AT) in percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction (STEMI) has not proved effective in randomized trials. However, in patients undergoing primary percutaneous coronary intervention with severely reduced flow or visible thrombus, AT remains an intuitively attractive option. The use of adjunctive AT in a high-risk cohort of 158 consecutive patients with STEMI and Thrombolysis In Myocardial Infarction (TIMI) 0 to 1 flow or visible thrombus on baseline angiography was examined. Of these, 80 patients underwent AT as an adjunct to primary percutaneous coronary intervention, and 78 underwent percutaneous coronary intervention without AT (non-AT). TIMI 3 flow rates, residual thrombus after percutaneous coronary intervention, and major adverse cardiac events (mortality and nonfatal Q-wave myocardial infarction) at 30 days, 6 months, and 1 year were compared. Baseline characteristics were similar between groups. The AT group more frequently achieved TIMI 3 flow after the intervention (91.3% AT vs 67.9% non-AT; p <0.001) and had less residual thrombus (7.5% AT vs 19.2% non-AT; p = 0.03). AT was associated with reduced major adverse cardiac events at 6 months (6.8% AT vs 24.0% non-AT; p = 0.004) and 1 year (16.6% AT vs 29.2% non-AT; p = 0.009), and decreased mortality rates in the AT group at 6 months (5.4% AT vs 21.3% non-AT; p = 0.004) and 1 year (7.7% AT vs 26.2% non-AT; p = 0.005). In conclusion, for patients with STEMI and TIMI 0 or 1 flow or visible thrombus on baseline angiography, AT was associated with increased TIMI 3 flow rates, decreased residual thrombus, and decreased clinical events, including mortality.

Impact of "off-label" utilization of drug-eluting stents on clinical outcomes in patients undergoing percutaneous coronary intervention.

The utilization of drug-eluting stents (DES) in "real world" practice has deviated from Food and Drug Administration-approved indications. Safety concerns have arisen from recent reports that suggested increased mortality and nonfatal myocardial infarction (MI) with DES usage. Little is known about the clinical outcomes of patients undergoing intracoronary DES implantation for unapproved indications as a group compared with outcomes after bare metal stent (BMS) placement. The clinical outcomes of 546 patients undergoing DES implantation for >or=1 non-Food and Drug Administration-approved ("off label") indication since the approval of the device were assessed. The group was then matched by propensity score with 546 patients receiving BMSs prior to DES approval for the same indications. The primary endpoint was major adverse cardiac events (cardiac death, nonfatal Q-wave myocardial infarction [MI], and target vessel revascularization) at 12 months. Baseline clinical and angiographic characteristics were well matched between BMS and DES groups. The use of debulking devices was higher in the BMS group. Patients in the BMS group were more likely to be treated with larger diameter and shorter stents. There was no significant difference in the rate of in-hospital and 30-day adverse cardiac events. At 12 months, the primary endpoint of major adverse cardiac events was significantly reduced in the DES group (23.6% vs 16.7%, p=0.004), driven by reductions in the need for repeat revascularization (target lesion revascularization: 16.4% vs 7.8%, p<0.001; target vessel revascularization: 20.2% vs 13.1%, p=0.003). There was no significant difference in freedom from cardiac death or nonfatal Q-wave MI between groups (p=0.27). In conclusion, the utilization of DES for non-Food and Drug Administration-approved indications proved to be efficacious and safe when compared with a BMS cohort matched by propensity score. The advantage for DES was driven by reductions in repeat revascularization. "Off-label" DES use was not associated with increased rates of cardiac death and nonfatal MI at 12 months.