Asymptomatic left ventricular dysfunction (ALVD) is present in 3-6% of the general population, is associated with reduced quality of life and longevity, and is treatable when found
. An inexpensive, ...noninvasive screening tool for ALVD in the doctor's office is not available. We tested the hypothesis that application of artificial intelligence (AI) to the electrocardiogram (ECG), a routine method of measuring the heart's electrical activity, could identify ALVD. Using paired 12-lead ECG and echocardiogram data, including the left ventricular ejection fraction (a measure of contractile function), from 44,959 patients at the Mayo Clinic, we trained a convolutional neural network to identify patients with ventricular dysfunction, defined as ejection fraction ≤35%, using the ECG data alone. When tested on an independent set of 52,870 patients, the network model yielded values for the area under the curve, sensitivity, specificity, and accuracy of 0.93, 86.3%, 85.7%, and 85.7%, respectively. In patients without ventricular dysfunction, those with a positive AI screen were at 4 times the risk (hazard ratio, 4.1; 95% confidence interval, 3.3 to 5.0) of developing future ventricular dysfunction compared with those with a negative screen. Application of AI to the ECG-a ubiquitous, low-cost test-permits the ECG to serve as a powerful screening tool in asymptomatic individuals to identify ALVD.
Objectives The aim of this study was to determine the relationship between B-type natriuretic peptide (BNP) and survival in patients with hypertrophic cardiomyopathy. Background Natriuretic peptides ...are released in response to neurohormonal activation, myocardial stretch, and wall tension and therefore reflect hemodynamic derangements. Methods A total of 772 patients with hypertrophic cardiomyopathy had BNP obtained in conjunction with echocardiography and clinical evaluation, inclusive of cardiopulmonary exercise evaluation in 429 patients (56%). Results Survival free of all-cause mortality was lower across increasing levels of BNP (log-rank test, p = 0.002). Three-year survival by tertile was 99.2% (95% confidence interval: 94.3% to 99.9%; BNP level ≤98 pg/ml), 94.8% (95% confidence interval: 88.2% to 97.8%; BNP level, >98 to <298 pg/ml), and 89.9% (95% confidence interval: 82.0% to 94.5%; BNP level ≥298 pg/ml). Compared with patients in the first tertile, the hazard ratios for death in the second and third tertiles were 4.88 (p = 0.006) and 6.98 (p = 0.0003), respectively. This relationship persisted in patients without resting obstructive physiology (n = 497, p = 0.01). BNP levels were related to New York Heart Association functional status (p < 0.0001) and the subsequent need for septal reduction therapy in follow-up (p = 0.04). Conclusions In this large cohort of patients with hypertrophic cardiomyopathy, BNP was an independent predictor of morbidity and mortality.
Objectives Our objective was to determine the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) for death and cardiovascular events among subjects without risk factors ...for heart failure (HF), which we term healthy normal. Background Previous studies report that plasma NT-proBNP has prognostic value for cardiovascular events in the general population even in the absence of HF. It is unclear if NT-proBNP retains predictive value in healthy normal subjects. Methods We identified a community-based cohort of 2,042 subjects in Olmsted County, Minnesota. Subjects with symptomatic (stage C/D) HF were excluded. The remaining 1,991 subjects underwent echocardiography and NT-proBNP measurement. We further defined healthy normal (n = 703) and stage A/B HF (n = 1,288) subgroups. Healthy normal was defined as the absence of traditional clinical cardiovascular risk factors and echocardiographic structural cardiac abnormalities. Subjects were followed for death, HF, cerebrovascular accident, and myocardial infarction with median follow-up of 9.1, 8.7, 8.8, and 8.9 years, respectively. Results NT-proBNP was not predictive of death or cardiovascular events in the healthy normal subgroup. Similar to previous reports, in stage A/B HF, plasma NT-proBNP values greater than age-/sex-specific 80th percentiles were associated with increased risk of death, HF, cerebrovascular accident, and myocardial infarction (p < 0.001 for all) even after adjustment for clinical risk factors and structural cardiac abnormalities. Conclusions These findings do not support the use of NT-proBNP as a cardiovascular biomarker in healthy normal subjects and have important implications for NT-proBNP–based strategies for early detection and primary prevention of cardiovascular disease.
High-sensitivity cardiac troponin (hs-cTn) assays are now available that can detect measurable troponin in significantly more individuals in the general population than conventional assays. The ...clinical use of these hs-cTn assays depends on the development of proper reference values. Therefore, our objective was to define hs-cTnI reference values and determinants in the general community, in a healthy reference cohort, and in subsets with diseases.
A well-characterized community-based cohort of 2042 study participants underwent clinical assessment and echocardiographic evaluation. Baseline hs-cTnI measurements were obtained in 1843 individuals. A healthy reference cohort (n = 565) without cardiac, renal, or echocardiographic abnormalities was identified.
Measurable hs-cTnI was identified in 1716 (93%) of the community-based study cohort and 499 (88%) of the healthy reference cohort. Parameters that significantly contributed to higher hs-cTnI concentrations in the healthy reference cohort included age, male sex, systolic blood pressure, and left ventricular mass. Glomerular filtration rate and body mass index were not independently associated with hs-cTnI in the healthy reference cohort. Individuals with diastolic and systolic dysfunction, hypertension, and coronary artery disease (but not impaired renal function) had significantly higher hs-cTnI values than the healthy reference cohort.
We assessed an hs-cTnI assay with the aid of echocardiographic imaging in a large, well-characterized community-based cohort. hs-cTnI is remarkably sensitive in the general population, and there are important sex and age differences among healthy reference individuals. These results have important implications for defining hs-cTnI reference values and identifying disease.
Objectives We sought to define the cardiometabolic phenotype associated with rs5068, a genetic variant of the atrial natriuretic peptide (ANP) gene. Background The ANP and B-type natriuretic peptide ...play an important role in cardiorenal homeostasis but also exert metabolic actions. Methods We genotyped 1,608 randomly selected residents from Olmsted County, Minnesota. Subjects were well-characterized. Results Genotype frequencies were: AA 89.9%, AG 9.7%, and GG 0.4%; all subsequent analyses were AA versus AG+GG. The G allele was associated with increased plasma levels of N-terminal pro-atrial natriuretic peptide (p = 0.002), after adjustment for age and sex. The minor allele was also associated with lower body mass index (BMI) (p = 0.006), prevalence of obesity (p = 0.002), waist circumference (p = 0.021), lower levels of C-reactive protein (p = 0.027), and higher values of high-density lipoprotein cholesterol (p = 0.019). The AG+GG group had a lower systolic blood pressure (p = 0.011) and lower prevalence of myocardial infarction (p = 0.042). The minor allele was associated with a lower prevalence of metabolic syndrome (p = 0.025). The associations between the G allele and high-density lipoprotein cholesterol, C-reactive protein values, myocardial infarction, and metabolic syndrome were not significant, after adjusting for BMI; the associations with systolic blood pressure, BMI, obesity, and waist circumference remained significant even after adjusting for N-terminal pro-atrial natriuretic peptide. Conclusions In a random sample of the general U.S. population, the minor allele of rs5068 is associated with a favorable cardiometabolic profile. These findings suggest that rs5068 or genetic loci in linkage disequilibrium might affect susceptibility for cardiometabolic diseases and support the possible protective role of natriuretic peptides by their favorable effects on metabolic function. Replication studies are needed to confirm our findings.
High-sensitivity cardiac troponin assays have potent prognostic value in stable cardiovascular disease cohorts. Our objective was to assess the prognostic utility of a novel cardiac troponin I (cTnI) ...high-sensitivity assay, independently and in combination with amino-terminal pro-B-type natriuretic peptide (NT-proBNP), for the future development of heart failure and mortality in the general community.
A well-characterized community-based cohort of 2042 participants underwent clinical assessment and echocardiographic evaluation. Baseline measurements of cTnI with a high-sensitivity assay and NT-proBNP were obtained in 1843 individuals. Participants were followed for new-onset heart failure and mortality with median (25th, 75th percentile) follow-up of 10.7 (7.9, 11.6) and 12.1 (10.4, 13.0) years, respectively.
When measured with a high-sensitivity assay, cTnI greater than the sex-specific 80th percentile was independently predictive of heart failure hazard ratio 2.56 (95% confidence interval 1.88-3.50), P < 0.001 and mortality 1.91(1.49-2.46), P < 0.001 beyond conventional risk factors in this community-based cohort, with significant increases in the net reclassification improvement for heart failure. The prognostic utility of cTnI measured with a high-sensitivity assay goes beyond NT-proBNP, yet our data suggest that these 2 assays are complementary and most beneficial when evaluated together in identifying at-risk individuals in the community.
Our findings lay the foundation for prospective studies aimed at identification of individuals at high risk by use of a multimarker approach, followed by aggressive prevention strategies to prevent subsequent heart failure.
To determine whether chronic phosphodiesterase-V (PDEV) inhibition with tadalafil will improve urinary sodium excretion, glomerular filtration rate (GFR), plasma cyclic guanosine 3’, 5’-monophosphate ...(cGMP), and urinary cGMP excretion in response to volume expansion (VE) in patients with preclinical diastolic dysfunction (PDD) or stage B heart failure.
PDD is defined as abnormal diastolic function with normal systolic function, without clinical heart failure. PDD is predictive of development of heart failure and all-cause mortality. Impaired renal function and attenuated cGMP response to VE are hallmarks of PDD.
A double-blind, placebo-controlled, proof-of-concept study was conducted to compare 12 weeks of tadalafil 20 mg daily (n = 14) vs placebo (n = 7). Subjects underwent 2 study visits 12 weeks apart. Renal, neurohormonal and echocardiographic assessments were performed before and after intravascular VE (normal saline 0.25 mL/kg/min for 1 hour).
Baseline characteristics were similar. There was no increase in GFR, plasma cGMP or urinary cGMP excretion in response to VE in either group at visit 1. At visit 2, tadalafil did not result in significant change in GFR but increased plasma cGMP and urinary cGMP excretion at baseline. In response to VE, tadalafil resulted in increased urine flow, urinary sodium excretion, GFR (7.00 -1.0, 26.3 vs -9.00 -24.5, 2.0 mL/min/1.73m2; P = 0.02) and plasma cGMP (0.50 -0.1, 0.7 vs -0.25 -0.6, -0.1 pmol/mL; P = 0.02). It did not improve urinary cGMP excretion after VE.
In PDD, chronic PDEV inhibition with tadalafil improved renal response to VE through increased urine flow, urinary sodium excretion, GFR, and plasma cGMP. Further studies are required to determine whether this enhanced renal response can mitigate progression to clinical heart failure.
Natriuretic peptides (NPs) are cardioprotective through the activation of guanylyl cyclase (GC) receptors A and B. CD-NP, also known as cenderitide, is a novel engineered NP that was designed to ...uniquely serve as a first-in-class dual GC receptor agonist. Recognizing the aldosterone suppressing actions of GC-A activation and the potent inhibitory actions on collagen synthesis and fibroblast proliferation through GC-B activation, the current study was designed to establish the anti-fibrotic actions of CD-NP, administered subcutaneously, in an experimental rat model of early cardiac fibrosis induced by unilateral nephrectomy (UNX). Our results demonstrate that a two week subcutaneous infusion of CD-NP significantly suppresses left ventricular fibrosis and circulating aldosterone, while preserving both systolic and diastolic function, in UNX rats compared to vehicle treated UNX rats. Additionally we also confirmed, in vitro, that CD-NP significantly generates the second messenger, cGMP, through both the GC-A and GC-B receptors. Taken together, this novel dual GC receptor activator may represent an innovative anti-fibrotic therapeutic agent.
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