Development and Validation of a Electrocardiographic Diagnostic Score of Heart Failure Among Patients with Hypertension Attending a Tertiary Hospital in Ibadan, Nigeria: The RISK-HHF Case-Control Study

Abstract

Objectives: Hypertension is the leading cause of HF in sub-Saharan Africa. Electrocardiography (ECG) is a cheap and easily available stratification tool for the diagnosis and prognostication of individuals with hypertension. The aim of this study was to develop an ECG-based HF diagnostic score among patients with hypertension attending a specialist cardiology clinic.

Methods: One hundred and one (101) case-control age- and sex-matched pairs were recruited. The study population were adults with a clinical diagnosis of hypertensive HF failure (cases) and systemic hypertension without HF (controls). Participants underwent clinical assessment and ECG. Associations between ECG variables and HF risk were tested with chi square test. Logistic regression modelling (age- and sex adjusted) was trained on a random subset of participants and tested on the remaining participants to determine the ECG abnormalities that are diagnostic of HF and develop a HF diagnostic score. The HF diagnostic score was then validated in an independent dataset of the ECG-Hypertension Audit. Goodness of fit and c-statistics of the HF summed diagnostic score in the training, testing and validation datasets are presented. A two-sided p value of <0.05 was considered statistically significant.

Results: The independent ECG diagnostic markers of HF among hypertensive patients in this study in decreasing order of effect size were sinus tachycardia (aOR: 7.72, 95% CI: 2.31-25.85). arrhythmia (aOR: 7.14, 95% CI: 2.57-19.86), left ventricular hypertrophy (aOR: 4.47; 1.85-10.77) and conduction abnormality (aOR: 3.41, 95% CI: 1.21-9.65). The HF summed diagnostic score showed excellent calibration and discrimination in the training (Hosmer Lemeshow p = 0.90; c-statistic 0.82; 95% CI 0.76-0.89) and test samples (Hosmer Lemeshow p=0.31; c-statistic 0.73 95% CI 0.60 to 0.87) of the derivation cohort and an independent validation audit cohort (Hosmer Lemeshow p = 0.17; c-statistic 0.79 95% CI 0.74 to 0.84) respectively. The model showed high diagnostic accuracy in individuals with different intermediate pre-test probabilities of HF.

Conclusions: A ECG based HF score consisting of sinus tachycardia, arrhythmia, conduction abnormality and left ventricular hypertrophy is diagnostic of HF especially in those with intermediate pre-test probability of HF. This has clinical importance in the stratification of individuals with systemic hypertension.

Keywords: Arrhythmia; Conduction abnormalities; Hypertensive HF; Left ventricular hypertrophy; Sinus tachycardia.

Fig. 1

Multivariable logistic regression model of electrocardiographic patterns in the training dataset (Odds ratios are age- and sex adjusted). In the reference population with no sinus tachcyardia, arrhythmia, conduction abnormality or LVH, the odds ratio of HF (i.e the intercept) was 0.09 (95%CI 0.01, 0.81).

Fig. 2

ROCs curve of the regression model (xb) and the derived HF summed diagnostic rule score with c-statistics of training dataset of random sample of 152 participants; p value for equality of ROCs = 0.54 (Hosmer–Lemeshow statistic for goodness of fit of model p = 0.90 for regression model; Hosmer–Lemeshow statistic for goodness of fit of the HF prediction score p = 0.95 for regression model).

Fig. 3

HF summed diagnostic rule score performance in the test dataset of 50 participants (Hosmer–Lemeshow statistic for goodness of fit of model p = 0.31; c statistic 0.73, 95%CI of c-statistic 0.60, 0.87).

Fig. 4

HF summed diagnostic rule score performance using k-fold cross validation in the whole RISK-HHF dataset of 202 participants (Boot-strapped bias corrected 95%CI of c-statistic 0.70, 0.84) Hosmer–Lemeshow statistic for goodness of fit of model p = 0.85.

Fig. 5

Relationship of HF summed diagnostic rule score with probability of presence of heart failure in the whole RISK-HHF dataset.

Fig. 6

HF summed diagnostic rule score performance in the ECG-Hypertension Audit dataset (95%CI of c-statistic 0.74, 0.84).

Fig. 7

HF summed diagnostic rule score performance using K fold cross validation in the ECG-Hypertension Audit dataset (Bootstrapped bias corrected 95%CI interval of c-statistic 0.68, 0.80) Hosmer–Lemeshow statistic for goodness of fit of model p = 0.17.