Ambulatory and silent myocardial ischemia in women with coronary microvascular dysfunction: Results from the Cardiac Autonomic Nervous System study (CANS).

BACKGROUND: Up to two-thirds of patients with obstructive coronary artery disease (CAD) have silent ischemia (SI), which predicts an adverse prognosis and can be a treatment target in obstructive CAD. Over 50% of women with ischemia and no obstructive CAD have coronary microvascular dysfunction (CMD), which is associated with adverse cardiovascular outcomes. We aimed to investigate the prevalence of SI in CMD in order to consider it as a potential treatment target. METHODS: 36 women with CMD by coronary reactivity testing and 16 age matched reference subjects underwent 24-h 12-lead ambulatory ECG monitoring (Mortara Instruments) after anti-ischemia medication withdrawal. Ambulatory ECG recordings were reviewed by two-physician consensus masked to subject status for SI measured by evidence of ≥1 minute horizontal or downsloping ST segment depression ≥1.0 mm, measured 80 ms from the J point. RESULTS: Demographics, resting heart rate, and systolic blood pressure were similar between CMD and reference subjects. Thirty-nine percent of CMD women had a total of 26 SI episodes vs. 0 episodes in the reference group (p = 0.002). Among these women 13/14 (93%) had SI, and few episodes (3/26, 12%) were symptomatic. Mean HR at the onset of SI was 96 ±â€¯13 bpm and increased to 117 ±â€¯16 bpm during the ischemic episodes. 87% reported symptoms that were not associated with ST depressions. CONCLUSIONS: Ambulatory ischemia is prevalent in women with CMD, with a majority being SI, while most reported symptoms were not accompanied by ambulatory ischemia. Clinical trials evaluating anti-ischemic medications should be considered in the CMD population.

Maladaptive left ventricular remodeling in women: An analysis from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study.

BACKGROUND: Women represent approximately half of heart failure hospitalizations and are disproportionately affected by heart failure with preserved ejection fraction (HFpEF). Women with signs and symptoms of ischemia, preserved left ventricular ejection fraction (LVEF), and no obstructive coronary artery disease (CAD) often have elevated left ventricular end-diastolic pressure (LVEDP). However, isolated elevated LVEDP in the absence of coronary microvascular dysfunction (CMD) is not understood. METHODS: Among 244 women with signs and symptoms of ischemia, no obstructive CAD, and preserved LVEF who underwent invasive coronary reactivity testing (CRT), 43 (18%) women had no evidence of CMD. LVEDP was measured at time of CRT, and left ventricular (LV) volumes and mass were assessed by cardiac magnetic resonance (CMR) imaging. RESULTS: Of the 43 women without CMD, 24 (56%) had elevated LVEDP [mean 18 mm Hg (SD = 3)] compared to 19 (44%) with normal LVEDP [11 mm Hg (SD = 3)]. The elevated LVEDP group had a comparatively higher systolic and diastolic blood pressure, lower LV end-diastolic volume index (EDVI), and higher mass-to-volume ratio. Other functional parameters were not significantly different. CONCLUSIONS: Among women with signs and symptoms of ischemia without obstructive CAD, absence of CMD, and preserved LVEF, isolated elevated LVEDP is associated with a significantly higher systolic and diastolic blood pressure, higher LV mass-to-volume ratio and lower LV EDVI. These results suggest these women have maladaptive remodeling to blood pressure. Given the relatively high prevalence of HFpEF in women, these hypothesis-generating results suggest that further study of ventricular remodeling is warranted.

Electrical risk score beyond the left ventricular ejection fraction: prediction of sudden cardiac death in the Oregon Sudden Unexpected Death Study and the Atherosclerosis Risk in Communities Study.

AIMS: There is an urgent need to extend sudden cardiac death (SCD) risk stratification beyond the left ventricular ejection fraction (LVEF). We evaluated whether a cumulative electrocardiogram (ECG) risk score would improve identification of individuals at high risk of SCD. METHODS AND RESULTS: In the community-based Oregon Sudden Unexpected Death Study (catchment population ∼1 million), 522 SCD cases with archived 12-lead ECG available (65.3 ± 14.5 years, 66% male) were compared with 736 geographical controls to assess the incremental value of multiple ECG parameters in SCD prediction. Heart rate, LV hypertrophy, QRS transition zone, QRS-T angle, QTc, and Tpeak-to-Tend interval remained significant in the final model, which was externally validated in the Atherosclerosis Risk in Communities (ARIC) Study. Sixteen percent of cases and 3% of controls had ≥4 abnormal ECG markers. After adjusting for clinical factors and LVEF, increasing ECG risk score was associated with progressively greater odds of SCD. Overall, subjects with ≥4 ECG abnormalities had an odds ratio (OR) of 21.2 for SCD [95% confidence interval (CI) 9.4-47.7; P < 0.001]. In the LVEF >35% subgroup, the OR was 26.1 (95% CI 9.9-68.5; P < 0.001). The ECG risk score increased the C-statistic from 0.625 to 0.753 (P < 0.001), with net reclassification improvement of 0.319 (P < 0.001). In the ARIC cohort validation, risk of SCD associated with ≥4 ECG abnormalities remained significant after multivariable adjustment (hazard ratio 4.84; 95% CI 2.34-9.99; P < 0.001; C-statistic improvement 0.759-0.774; P = 0.019). CONCLUSION: This novel cumulative ECG risk score was independently associated with SCD and was particularly effective for LVEF >35% where risk stratification is currently unavailable. These findings warrant further evaluation in prospective clinical investigations.

The Romhilt-Estes electrocardiographic score predicts sudden cardiac arrest independent of left ventricular mass and ejection fraction.

BACKGROUND: The Romhilt-Estes point score system (RE) is an established ECG criterion for diagnosing left ventricular hypertrophy (LVH). In this study, we assessed for the first time, whether RE and its components are predictive of sudden cardiac arrest (SCA) independent of left ventricular (LV) mass. METHODS: Sudden cardiac arrest (SCA) cases occurring between 2002 and 2014 in a Northwestern US metro region (catchment area approx. 1 million) were compared to geographic controls. ECGs and echocardiograms performed prior to the SCA and those of controls were acquired from the medical records and evaluated for the ECG criteria established in the RE score and for LV mass. RESULTS: Two hundred forty-seven SCA cases (age 68.3 ± 14.6, male 64.4%) and 330 controls (age 67.4 ± 11.5, male 63.6) were included in the analysis. RE scores were greater in cases than controls (2.5 ± 2.1 vs. 1.9 ± 1.7, p < .001), and SCA cases were more likely to meet definite LVH criteria (18.6% vs. 7.9%, p < .001). In a multivariable model including echocardiographic LVH and LV function, definite LVH remained independently predictive of SCA (OR 2.04, 95% CI 1.16-3.59, p = .013). The model was replicated with the individual ECG criteria, and only SV1.2  ≥ 30 mm and delayed intrinsicoid deflection remained significant predictors of SCA. CONCLUSION: Left ventricular hypertrophy (LVH) as defined by the RE point score system is associated with SCA independent of echocardiographic LVH and reduced LV ejection fraction. These findings support an independent role for purely electrical LVH, in the genesis of lethal ventricular arrhythmias.

Delayed intrinsicoid deflection of the QRS complex is associated with sudden cardiac arrest.

BACKGROUND: Prolongation of initial ventricular depolarization on the 12-lead electrocardiogram (ECG), or delayed intrinsicoid deflection (DID), can indicate left ventricular hypertrophy (LVH). The possibility that this marker could convey distinct risk of sudden cardiac arrest (SCA) has not been evaluated. OBJECTIVE: To evaluate the association of DID and SCA in the community. METHODS: In the ongoing prospective, population-based Oregon Sudden Unexpected Death Study (Oregon SUDS; catchment area approximately 1 million), SCA cases were compared to geographic controls with no SCA. Archived ECGs (closest and unrelated to SCA event for cases) were evaluated for the presence of DID, defined as ≥0.05 second in leads V5 or V6. Left ventricular (LV) mass and function were evaluated from archived echocardiograms. RESULTS: SCA cases (n = 272, 68.7 ± 14.6 years, 63.6% male) as compared to controls (n = 351, 67.6 ± 11.4 years, 63.3% male) were more likely to have DID on ECG (28.3% vs. 17.1%, P = .001). DID was associated with increased SCA odds (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.31-2.81; P = .001), but showed poor correlation with LV mass and echocardiographic LVH (kappa 0.13). In multivariate analysis adjusted for clinical and ECG markers, reduced LV ejection fraction, and echocardiographic LVH, DID remained an independent predictor of SCA (OR 1.82; 95% CI 1.12-2.97; P = .016). Additionally, in a sensitivity analysis restricted to narrow QRS, DID and ECG LVH by voltage were each independently associated with SCA risk. CONCLUSION: DID was associated with increased SCA risk independent of echocardiographic LVH, ECG LVH, and reduced LV ejection fraction, potentially reflecting unique electrical remodeling that warrants further investigation.