Percutaneous coronary intervention in insulin‐treated diabetic patients: A meta‐analysis

BackgroundThis meta‐analysis of randomized controlled trials (RCTs) compared long‐term adverse clinical outcomes of percutaneous coronary intervention (PCI) in insulin‐treated diabetes mellitus (ITDM) and non‐ITDM patients.MethodsThis is a meta‐analysis study. The PubMed and Embase databases were searched for articles on long‐term adverse clinical outcomes of PCI in ITDM and non‐ITDM patients. The risk ratios (RR) and 95% confidence intervals (CI) were calculated.ResultsA total of 11 related RCTs involving 8853 DM patients were included. Compared with non‐ITDM patients, ITDM patients had significantly higher all‐cause mortality (ACM) (RR = 1.52, 95% CI: 1.25–1.85, p _{heterogeneity} = .689, I ² = 0%), major adverse cardiac and cerebrovascular events (MACCE) (RR = 1.35, 95% CI: 1.18–1.55, p _{heterogeneity} = .57, I ² = 0%), myocardial infarction (MI) (RR = 1.41, 95% CI: 1.16–1.72, p _{heterogeneity} = .962, I ² = 0%), and stent thrombosis (ST) (RR = 1.75, 95% CI: 1.23–2.48, p _{heterogeneity} = .159, I ² = 32.4%). No significant difference was found in the target lesion revascularization (TLR) and target vessel revascularization (TVR) between the ITDM and non‐ITDM groups.ConclusionsThe results showed that ITDM patients had significantly higher ACM, MACCE, MI, and ST, compared with non‐ITDM patients.     

Fragmented QRS is associated with ventricular arrhythmias in heart failure patients: A systematic review and meta‐analysis

IntroductionMany primary prevention heart failure (HF) patients with an implantable cardiac defibrillator (ICD) rarely experience life‐threatening ventricular arrhythmias (VA). New strategies are required to identify patients most at risk of VA and sudden cardiac death who would benefit from an ICD. One potential method is the detection of fragmented QRS (fQRS) on the electrocardiogram. The aim was to assess the predictive capacity of fQRS for VA and mortality in ischemic (ICM) and non‐ischemic cardiomyopathy (NICM) primary prevention HF patients.Methods and ResultsA systematic review and meta‐analysis of studies examining fQRS in HF patients with or without an ICD who met primary prevention indications with reduced ejection fraction ≤40%. Outcome measures were VA (or appropriate ICD therapy) and all‐cause mortality. Ten studies involving 3885 patients were included for analysis. Most patients were male with non‐fQRS patients being significantly younger (−1.5[−2.66, −0.42], p = .03). Diabetes was more likely in fQRS patients (1.12[1.01, 1.25], p = .03) while non‐fQRS patients were 28% more likely to have a history of atrial fibrillation (0.82[0.67,1.00], p = .05). Ventricular arrhythmias were significantly 1.5 times more likely in patients with fQRS (1.51[1.02, 2.25], p = .04). HF patients were 1.7 times more likely to die of any cause if fQRS was present (1.68[1.13, 2.52], p = .01). NICM patients with fQRS have a significant 2.6‐fold increased incidence of death compared with ICM patients (2.55[1.63, 3.98], p < .0001).ConclusionfQRS is associated with VA and all‐cause mortality and may be a novel marker in the risk stratification of primary prevention HF patients indicated for ICD implantation.     

Predictive impacts of chronic kidney disease and cardiac sympathetic nervous activity on lethal arrhythmic events in chronic heart failure

BackgroundThe clinical implications of chronic kidney disease (CKD) and cardiac sympathetic nervous activity (CSNA) regarding lethal arrhythmic events have not yet been fully elucidated in patients with chronic heart failure (CHF). We hypothesized that the combination of CKD and abnormal CSNA, assessed by ¹²³I‐metaiodobenzylguanidine (¹²³I‐MIBG) scintigraphy, may provide useful prognostic information for lethal arrhythmic events.MethodsWe studied 165 consecutive hospitalized CHF patients without dialysis. Cardiac ¹²³I‐MIBG scintigraphy was performed in a clinically stable condition, and abnormal CSNA was defined as a late heart‐to‐mediastinum ratio of <1.6. CKD was defined as an estimated glomerular filtration rate of <60 ml/min/1.73 m². We then investigated the incidence of lethal arrhythmic events (sustained ventricular tachyarrhythmia, appropriate implantable cardioverter‐defibrillator therapy, or sudden cardiac death).ResultsDuring a median follow‐up of 5.3 years, lethal arrhythmic events were observed in 40 patients (24.2%). The patients were divided into four groups according to the presence of CKD and CSNA abnormality: non‐CKD/normal CSNA (n = 52), CKD/normal CSNA (n = 39), non‐CKD/abnormal CSNA (n = 33), and CKD/abnormal CSNA (n = 41). Kaplan–Meier analysis showed that CKD/abnormal CSNA had the highest event rate (log‐rank p = .004). Additionally, the Cox proportional hazard analysis revealed that CKD/abnormal CSNA was a predictor for lethal arrhythmic events compared with non‐CKD/normal CSNA (hazard ratio, 5.368, p = .001). However, the other two groups did not show significant differences compared with the non‐CKD/normal CSNA group.ConclusionsThe combination of CKD and abnormal CSNA, assessed by ¹²³I‐MIBG scintigraphy, had a high predictive value for lethal arrhythmic events in patients with CHF.     

Temporal variability of T‐wave morphology and risk of sudden cardiac death in patients with coronary artery disease

BackgroundThe possible relationship between temporal variability of electrocardiographic spatial heterogeneity of repolarization and the risk of sudden cardiac death (SCD) in patients with coronary artery disease (CAD) is not completely understood.MethodsThe standard deviation of T‐wave morphology dispersion (TMD‐SD), of QRST angle (QRSTA‐SD), and of T‐wave area dispersion (TW‐Ad‐SD) were analyzed on beat‐to‐beat basis from 10 min period of the baseline electrocardiographic recording in ARTEMIS study patients with angiographically verified CAD.ResultsAfter on average of 8.6 ± 2.3 years of follow‐up, a total of 66 of the 1,678 present study subjects (3.9%) had experienced SCD or were resuscitated from sudden cardiac arrest (SCA). TMD‐SD was most closely associated with the risk for SCD and was significantly higher in patients who had experienced SCD/SCA compared with those who remained alive (3.61 ± 2.83 vs. 2.64 ± 2.52, p = .008, respectively), but did not differ significantly between the patients who had experienced non‐SCD (n = 71, 4.2%) and those who remained alive (3.20 ± 2.73 vs. 2.65 ± 2.53, p = .077, respectively) or between the patients who succumbed to non‐cardiac death (n = 164, 9.8%) and those who stayed alive (2.64 ± 2.17 vs. 2.68 ± 2.58, p = .853). After adjustments with relevant clinical risk indicators of SCD/SCA, TMD‐SD still predicted SCD/SCA (HR 1.107, 95% CIs 1.035–1.185, p = .003).ConclusionsTemporal variability of electrocardiographic spatial heterogeneity of repolarization represented by TMD‐SD independently predicts long‐term risk of SCD/SCA in patients with CAD.     

Impact of revascularization in patients with post‐infarction left ventricular aneurysm and ventricular tachyarrhythmia

BackgroundVentricular arrhythmia is a leading cause of cardiac death among patients with post‐infarction left ventricular aneurysm (PI‐LVA). The effect of coronary revascularization in PI‐LVA patients with ventricular tachyarrhythmia remains unknown. This study aims to investigate the impact of revascularization therapy on clinical outcomes in these patients.MethodsA total of 238 PI‐LVA patients were enrolled, and 59 patients were presented with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). Patients were classified into 4 groups by treatment strategies (medical or revascularization) and the presence of VT/VF: group 1 (n = 57): VT/VF− and revascularization−; group 2 (n = 122): VT/VF− and revascularization+; group 3 (n = 34): VT/VF+ and revascularization+; and group 4 (n = 25): VT/VF+ and revascularization‐. The clinical outcomes were compared, and the primary endpoint was cardiac death or heart transplantation.ResultsPatients were followed up for 45 ± 16 months, and 41 patients (17.2%) reached the primary endpoint. Kaplan–Meier analysis showed that in VT/VF− patients, revascularization associated with higher cardiac survival compared with medical therapy (log‐rank p = .002), but in VT/VF+ patients, revascularization did not predict better cardiac outcome (log‐rank p = .901). Cox regression analysis revealed PET‐EF (HR 4.41, 95% CI: 1.72–11.36, p = .002) and moderate/severe mitral regurgitation (HR 2.32, 95% CI: 1.02–5.30, p = .046) as independent predictors of adverse cardiac outcome in patients with VT/VF.ConclusionPI‐LVA patients with VT/VF are at high risk of adverse cardiac outcome, and coronary revascularization does not mitigate this risk, although revascularization was associated with higher cardiac survival in PI‐LVA patients without VT/VF.     

Association between adiponectin‐to‐leptin ratio and heart rate variability in new‐onset paroxysmal atrial fibrillation: A retrospective cohort study

BackgroundThe adiponectin‐to‐leptin (A/L) ratio has been identified as a potential surrogate biomarker for metabolic disorders. However, it remains unknown whether the serum A/L ratio is associated with heart rate variability in paroxysmal atrial fibrillation (AF).MethodsFor this retrospective study, we included consecutive patients who underwent 24‐h long‐range electrocardiogram examination in our center for paroxysmal AF. The results of echocardiography, heart rate variability tests, and blood tests were also retrieved. Multivariate line regression analysis was performed to evaluate identify factors independently associated with heart rate variability.ResultsAmong the 85 included patients with paroxysmal AF, the median A/L ratio was 1.71. Univariate analysis indicated that patients with a low A/L ratio (<1.71, n = 42) had a lower high‐frequency (HF) power and a higher hs‐CRP level, low‐frequency (LF) power, and LF/HF ratio than those with a high A/L ratio (≥1.71, n = 43). Multivariate linear regression analysis showed that the serum leptin concentration was independently and positively associated with LF (β = 0.175, p = .028), while the serum adiponectin concentration was independently and positively associated with HF (β = 0.321, p = .001). Moreover, the A/L ratio was independently and negatively associated with the LF/HF ratio (β = −0.276, p = .007).ConclusionsThe A/L ratio was independently and negatively associated with the LF/HF ratio in patients with new‐onset paroxysmal AF.     

Long‐term outcomes in patients with normal coronary arteries,nonobstructive, or obstructive coronary artery disease on invasive coronary angiography

BackgroundNormal or near normal coronary arteries (NNCA) or nonobstructive coronary artery disease (CAD) are commonly found on invasive coronary angiography (ICA).HypothesisWe aimed to determine long‐term outcomes by severity of CAD in a contemporary cohort of patients undergoing ICA for evaluation for ischemic heart disease.MethodsWe assessed a consecutive cohort of 925 patients who underwent non‐emergent ICA over 24 months. Cardiac death (CD), nonfatal myocardial infarction (NFMI), late revascularization, and medication use were assessed.ResultsFollow‐up data was available in 850 patients. Of patients without heart failure, at a median of 6.0 years, there was a significant decrease in survival free from CD or NFMI, and from all cardiac events, for those with obstructive CAD compared with patients with NNCAs or nonobstructive CAD (p < .001 for both). No differences between NNCA and nonobstructive CAD patients in rates of CD or NFMI (2.0% vs. 2.1%/year, p = .58) or all cardiac events (2.4% vs. 2.9%/year, p = .84) were observed.ConclusionLong‐term follow‐up in a contemporary cohort of consecutive patients undergoing non‐emergent ICA for detection of CAD showed no difference in annual rates of CD or NFMI, or total cardiac events, in patients with NNCAs versus those with nonobstructive CAD, whereas patients with obstructive CAD had significantly more events. Event rates were low and similar by gender. Use of aspirin, lipid lowering therapy, and beta‐blockers increased in all subgroups after ICA. We speculate this may explain the low incidence of subsequent cardiac events, and similar event rates in patients with NNCA and nonobstructive CAD, even in patients presenting with non‐ST‐elevation MI.     

Comparison of coronary atherosclerotic disease burden between ST‐elevation myocardial infarction and non‐ST‐elevation myocardial infarction: Non‐culprit Gensini score and non‐culprit SYNTAX score

BackgroundPatients with non‐ST‐elevation myocardial infarction (NSTEMI) have worse long‐term prognoses than those with ST‐elevation myocardial infarction (STEMI).HypothesisIt may be attributable to more extended coronary atherosclerotic disease burden in patients with NSTEMI.MethodsThis study consisted of consecutive 231 patients who underwent coronary intervention for myocardial infarction (MI). To assess the extent and severity of atherosclerotic disease burden of non‐culprit coronary arteries, two scoring systems (Gensini score and synergy between percutaneous coronary intervention with Taxus and cardiac surgery [SYNTAX] score) were modified by subtracting the score of the culprit lesion: the non‐culprit Gensini score and the non‐culprit SYNTAX score.ResultsPatients with NSTEMI had more multi‐vessel disease, initial thrombolysis in myocardial infarction (TIMI) flow grade 2/3, and final TIMI flow grade 3 than those with STEMI. As compared to STEMI, patients with NSTEMI had significantly higher non‐culprit Gensini score (16.3 ± 19.8 vs. 31.2 ± 25.4, p < 0.001) and non‐culprit SYNTAX score (5.8 ± 7.0 vs. 11.1 ± 9.7, p < 0.001).ConclusionsPatients with NSTEMI had more advanced coronary atherosclerotic disease burden including non‐obstruction lesions, which may at least in part explain higher incidence of cardiovascular events in these patients.     

Proenkephalin and the risk of new‐onset heart failure: data from prevention of renal and vascular end‐stage disease

BackgroundEnkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new‐onset HF in the general population remains to be established.HypothesisWe hypothesized that plasma PENK concentrations are associated with new‐onset HF in the general population.MethodsWe included 6677 participants from the prevention of renal and vascular end‐stage disease study and investigated determinants of PENK concentrations and their association with new‐onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]).ResultsMedian PENK concentrations were 52.7 (45.1–61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT‐proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p < .001). After a median 8.3 (7.8–8.8) years follow‐up, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2–67.6) versus 52.7 (45.1–61.6) pmol/L, respectively (p = .003). In competing‐risk analyses, higher PENK concentrations were associated with higher risk of new‐onset HF (hazard ratio [HR] = 2.09[1.47–2.97], p < .001), including both HFrEF (HR = 2.31[1.48–3.61], p < .001) and HFpEF (HR = 1.74[1.02–2.96], p = .042). These associations were, however, lost after adjustment for eGFR.ConclusionsIn the general population, higher PENK concentrations were associated with lower eGFR and higher NT‐proBNP concentrations. Higher PENK concentrations were not independently associated with new‐onset HFrEF and HFpEF and mainly confounded by eGFR.     

T‐wave heterogeneity in standard resting 12‐lead ECGs is associated with 90‐day cardiac mortality in women following emergency department admission: A nested case–control study

BackgroundWe investigated whether T‐wave heterogeneity (TWH) can identify patients who are at risk for near‐term cardiac mortality.MethodsA nested case–control analysis was performed in the 888 patients admitted to the Emergency Department (ED) of our medical center in July through September 2018 who had ≥2 serial troponin measurement tests within 6 hr for acute coronary syndrome evaluation to rule‐in or rule‐out the presence of acute myocardial infarction. Patients who died from cardiac causes during 90 days after ED admission were considered cases (n = 20; 10 women) and were matched 1:4 on sex and age with patients who survived during this period (n = 80, 40 women). TWH, that is, interlead splay of T waves, was automatically assessed from precordial leads by second central moment analysis.ResultsTWH_V4‐6 was significantly elevated at ED admission in 12‐lead resting ECGs of female patients who died of cardiac causes during the following 90 days compared to female survivors (100 ± 14.9 vs. 40 ± 3.6 µV, p < .0001). TWH_V4‐6 generated areas under the receiver‐operating characteristic (ROC) curve (AUC) of 0.933 in women (p < .0001) and 0.573 in men (p = .4). In women, the ROC‐guided 48‐µV TWH_V4‐6 cut point for near‐term cardiac mortality produced an adjusted odds ratio of 121.37 (95% CI: 2.89–6,699.84; p = .02) with 100% sensitivity and 82.5% specificity. In Kaplan–Meier survival analysis, TWH_V4‐6 ≥ 48 µV predicted cardiac mortality in women during 90‐day follow‐up with a hazard ratio of 27.84 (95% CI: 7.29–106.36, p < .0001).ConclusionElevated TWH_V4‐6 is associated with near‐term cardiac mortality among women evaluated for acute coronary syndrome.     

Acute cardiovascular hospitalizations and illness severity before and during the COVID‐19 pandemic

BackgroundCardiovascular disease (CVD) hospitalizations declined worldwide during the COVID‐19 pandemic. It is unclear how shelter‐in‐place orders affected acute CVD hospitalizations, illness severity, and outcomes.HypothesisCOVID‐19 pandemic was associated with reduced acute CVD hospitalizations (heart failure [HF], acute coronary syndrome [ACS], and stroke [CVA]), and worse HF illness severity.MethodsWe compared acute CVD hospitalizations at Duke University Health System before and after North Carolina''s shelter‐in‐place order (January 1–March 29 vs. March 30–August 31), and used parallel comparison cohorts from 2019. We explored illness severity among admitted HF patients using ADHERE (“high risk”: >2 points) and GWTG‐HF (“>10%”: >57 points) in‐hospital mortality risk scores, as well as echocardiography‐derived parameters.ResultsComparing hospitalizations during January 1–March 29 (N = 1618) vs. March 30–August 31 (N = 2501) in 2020, mean daily CVD hospitalizations decreased (18.2 vs. 16.1 per day, p = .0036), with decreased length of stay (8.4 vs. 7.5 days, p = .0081) and no change in in‐hospital mortality (4.7 vs. 5.3%, p = .41). HF hospitalizations decreased (9.0 vs. 7.7 per day, p = .0019), with higher ADHERE (“high risk”: 2.5 vs. 4.5%; p = .030), but unchanged GWTG‐HF (“>10%”: 5.3 vs. 4.6%; p = .45), risk groups. Mean LVEF was lower (39.0 vs. 37.2%, p = .034), with higher mean LV mass (262.4 vs. 276.6 g, p = .014).ConclusionsCVD hospitalizations, HF illness severity, and echocardiography measures did not change between admission periods in 2019. Evaluating short‐term data, the COVID‐19 shelter‐in‐place order was associated with reductions in acute CVD hospitalizations, particularly HF, with no significant increase in in‐hospital mortality and only minor differences in HF illness severity.     

The value of ECG changes in risk stratification of COVID‐19 patients

BackgroundThere is growing evidence of cardiac injury in COVID‐19. Our purpose was to assess the prognostic value of serial electrocardiograms in COVID‐19 patients.MethodsWe evaluated 269 consecutive patients admitted to our center with confirmed SARS‐CoV‐2 infection. ECGs available at admission and after 1 week from hospitalization were assessed. We evaluated the correlation between ECGs findings and major adverse events (MAE) as the composite of intra‐hospital all‐cause mortality or need for invasive mechanical ventilation. Abnormal ECGs were defined if primary ST‐T segment alterations, left ventricular hypertrophy, tachy or bradyarrhythmias and any new AV, bundle blocks or significant morphology alterations (e.g., new Q pathological waves) were present.ResultsAbnormal ECG at admission (106/216) and elevated baseline troponin values were more common in patients who developed MAE (p = .04 and p = .02, respectively). Concerning ECGs recorded after 7 days (159), abnormal findings were reported in 53.5% of patients and they were more frequent in those with MAE (p = .001). Among abnormal ECGs, ischemic alterations and left ventricular hypertrophy were significantly associated with a higher MAE rate. The multivariable analysis showed that the presence of abnormal ECG at 7 days of hospitalization was an independent predictor of MAE (HR 3.2; 95% CI 1.2–8.7; p = .02). Furthermore, patients with abnormal ECG at 7 days more often required transfer to the intensive care unit (p = .01) or renal replacement therapy (p = .04).ConclusionsPatients with COVID‐19 should receive ECG at admission but also during their hospital stay. Indeed, electrocardiographic alterations during hospitalization are associated with MAE and infection severity.     

Association of non‐invasive electrocardiographic risk factors with left ventricular systolic function in post‐myocardial infarction patients with mildly reduced or preserved ejection fraction: Insights from the PRESERVE‐EF study

BackgroundElectrocardiographic non‐invasive risk factors (NIRFs) have an important role in the arrhythmic risk stratification of post‐myocardial infarction (post‐MI) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF). However, their specific relation to left ventricular systolic function remains unclear. We aimed to evaluate the association between NIRFs and LVEF in the patients included in the PRESERVE‐EF trial.MethodsWe studied 575 post‐MI ischemia‐free patients with LVEF≥40% (mean age: 57.0 ± 10.4 years, 86.2% men). The following NIRFs were evaluated: premature ventricular complexes, non‐sustained ventricular tachycardia (NSVT), late potentials (LPs), prolonged QTc, increased T‐wave alternans, reduced heart rate variability, and abnormal deceleration capacity with abnormal turbulence.ResultsThere was a statistically significant relationship between LPs (Chi‐squared = 4.975; p < .05), nsVT (Chi‐squared = 5.749, p < .05), PVCs (r= −.136; p < .01), and the LVEF. The multivariate linear regression analysis showed that LPs (p = .001) and NSVT (p < .001) were significant predictors of the LVEF. The results of the multivariate logistic regression analysis indicated that LPs (OR: 1.76; 95% CI: 1.02–3.05; p = .004) and NSVT (OR: 2.44; 95% CI: 1.18–5.04; p = .001) were independent predictors of the mildly reduced LVEF: 40%–49% versus the preserved LVEF: ≥50%.ConclusionLate potentials and NSVT are independently related to reduced LVEF while they are independent predictors of mildly reduced LVEF versus the preserved LVEF. These findings may have important implications for the arrhythmic risk stratification of post‐MI patients with mildly reduced or preserved LVEF.     

Automatically assessed P‐wave predicts cardiac events independently of left atrial enlargement in patients with cardiovascular risks: The Japan Morning Surge‐Home Blood Pressure Study

A prolonged P‐wave in electrocardiography (ECG) reflects atrial remodeling and predicts the development of atrial fibrillation (AF). The authors enrolled 810 subjects in the Japan Morning Surge Home Blood Pressure (J‐HOP) study who had ≥1 cardiovascular (CV) risk factor. The duration of P‐wave was automatically analyzed by standard 12‐lead electrocardiogram. Left atrial (LA) enlargement and left ventricular hypertrophy (LVH) were measured on echocardiography. The primary end points were fatal/nonfatal cardiac events: myocardial infarction, sudden death, and hospitalization for heart failure. The maximum P‐wave duration (Pmax) from the 12 leads was selected for analysis. The authors compared four prolonged P‐wave cutoffs (Pmax = 120, 130, 140, 150 ms) and cardiac events. LA diameter and left ventricular mass index (LVMI) were significantly associated with Pmax (r = 0.08, P = .02 and r = 0.17, P < .001, respectively). When the cutoff level was Pmax 120 or 130 ms, prolonged P‐wave was not associated with cardiac events (P = .45 and P = .10), but when a prolonged P‐wave was defined as Pmax ≥ 140 ms (n = 50) or Pmax ≥ 150 ms (n = 19), the patients in those groups had significantly higher incidence of cardiac events than others (P < .001 and P = .03). A Cox proportional hazards model including age, gender, body mass index, smoking, regular drinker, hypertension, dyslipidemia, diabetes, office systolic blood pressure, heart rate, LA enlargement, and LVH revealed that prolonged P‐wave defined as Pmax ≥ 140 ms was independently associated with cardiac events (hazard ratio: 4.23; 95% confidence interval: 1.30–13.77; P = .02). In conclusion, the automatically assessed prolonged P‐wave was associated with cardiac events independently of LA enlargement and LVH in Japanese patients with CV risks.     

Nocturnal blood pressure rather than night‐to‐day blood pressure ratio is related to arterial stiffening in untreated young and middle‐aged adults with non‐dipper hypertension

Little is known about nocturnal blood pressure (BP) or night‐to‐day BP ratio, which is a more specific determinant of arterial stiffness in subjects with non‐dipper hypertension? This study aims to investigate the correlation of nocturnal BP and brachial‐ankle pulse wave velocity (ba PWV), an index of arterial stiffness in untreated young and middle‐aged adults with non‐dipper hypertension.A cross‐sectional analysis of baseline parameters of the NARRAS trial was performed. Twenty‐four hour ambulatory BP measurements, ba PWV and routine clinical data collection were performed in all patients. The relationship of 24‐h ambulatory BP profiles, biochemical measures as well as demographic parameters and ba PWV were analyzed using Pearson''s correlation and multiple stepwise regression analysis.A total of 77 patients (mean age 47.0 ± 11.7 years) with non‐dipper hypertension were included. Age, height, weight and nocturnal systolic BP were related to ba PWV in Pearson''s correlation analysis. In stepwise regression analysis, age (β = 10.57, 95% confidence interval (CI): 6.099–15.042, p < 0.001) and weight (β = −3.835, 95% CI: −7.658‐−0.013, p = 0.049) are related to ba PWV. Nocturnal systolic BP (β = 8.662, 95% CI: 2.511–14.814, p = 0.006) was the independent predictors of ba PWV, even after night‐to‐day systolic BP ratio or 24‐h ambulatory BP profile were taken into account.Nocturnal systolic BP rather than night‐to‐day systolic BP ratio appears to be a more specific determinant for arterial stiffness, as assessed by ba PWV in young and middle‐aged adults with non‐dipper hypertension. 24‐h ambulatory BP measurements are essential for cardiovascular risk evaluation.     

Prediction of cardiovascular events using brachial‐ankle pulse wave velocity in hypertensive patients

The prognostic value of arterial stiffness in Korean hypertensive patients has not been specified. This study was performed to evaluate the prognostic value of brachial‐ankle pulse wave velocity (baPWV) in Korean hypertensive patients and to propose a cutoff value of baPWV predicting future cardiovascular events. A total of 2561 hypertensive patients without documented cardiovascular disease (mean age, 63 years; 47% females) who underwent baPWV measurement were retrospectively analyzed. Composite events of cardiac death, non‐fatal myocardial infarction, coronary revascularization, and ischemic stroke were assessed during the clinical follow‐up period. During a median follow‐up period of 4.14 years (interquartile range, 2.18‐5.48 years), there were 69 cases of composite events (2.7%). In receiver operating characteristic curve analysis, the best cutoff value of baPWV predicting composite events was 1630 cm/s (sensitivity, 79.7%; specificity, 49.1%; area under curve, 0.674; 95% confidence interval [CI], 0.613‐0.735; P < .001). In multivariable Cox regression analysis, higher baPWV (≥1630 cm/s) was independently associated with higher risk of the occurrence of composite events even after controlling for potential confounders (hazard ratio, 2.83; 95% confidence interval, 1.49‐5.36; P = .001). In conclusion, increased baPWV in Korean hypertensive patients was associated with an increased risk of future cardiovascular events. In addition, we suggested 1630 cm as a cutoff value of baPWV for predicting cardiovascular events, which will be helpful in guiding the treatment strategy of Korean hypertensive patients.     

Sodium–glucose cotransporter 2 inhibitor‐induced reduction in the mean arterial pressure improved renal composite outcomes in type 2 diabetes mellitus patients with chronic kidney disease: A propensity score‐matched model analysis in Japan

Aims/IntroductionLarge‐scale clinical trials have reported that, in patients with type 2 diabetes mellitus, sodium–glucose cotransporter 2 (SGLT2) inhibitor treatment affords favorable renal outcomes; the underlying mechanisms, however, remain unclear. Thus, this study investigated how SGLT2 inhibitor‐induced changes in the mean arterial pressure (MAP; denoted as ΔMAP) are associated with renal outcomes in type 2 diabetes mellitus patients with chronic kidney disease (CKD).Materials and MethodsWe retrospectively assessed the data of 624 Japanese type 2 diabetes mellitus patients with CKD who had been using SGLT2 inhibitors for >1 year. For propensity score matching (1:1 nearest neighbor match, with caliper value = 0.053, no replacement), patients were categorized into two groups based on the ΔMAP (>−4 mmHg [n = 329] and ≤−4.0 mmHg [n = 295]). Composite albuminuria progression or a ≥15% annual reduction in the estimated glomerular filtration rate was regarded as the end‐point.ResultsPer group, 173 propensity‐matched patients were compared. Patients with ΔMAP ≤−4 mmHg had a significantly lower incidence of composite renal outcomes than those with ΔMAP ≥−4 mmHg (5.8% [n = 10] vs 15.6% [n = 27], P = 0.003). Although the between‐group differences in the estimated glomerular filtration rates were non‐significant, patients with a ΔMAP ≤−4 mmHg had significantly larger reductions in the logarithmic urine albumin‐to‐creatinine ratio (P = 0.005).ConclusionsThe degree of blood pressure reduction after SGLT2 inhibitor treatment influenced renal composite outcomes in Japanese type 2 diabetes mellitus patients with CKD, confirming the importance of blood pressure management in type 2 diabetes mellitus patients with CKD, even when they are under SGLT2 inhibitor treatment.     

Noninvasive risk factors for the prediction of inducibility on programmed ventricular stimulation in post‐myocardial infarction patients with an ejection fraction ≥40% at risk for sudden cardiac arrest: Insights from the PRESERVE‐EF study

BackgroundIn the PRESERVE‐EF study, a two‐step sudden cardiac death (SCD) risk stratification approach to detect post‐myocardial infarction (MI) patients with left ventricle ejection fraction (LVEF) ≥40% at risk for major arrhythmic events (MAEs) was used. Seven noninvasive risk factors (NIRFs) were extracted from a 24‐h ambulatory electrocardiography (AECG) and a 45‐min resting recording. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS) and inducible patients received an Implantable Cardioverter ‐ Defibrillator (ICD).MethodsIn the present study, we evaluated the performance of the NIRFs, as they were described in the PRESERVE‐EF study protocol, in predicting a positive PVS. In the PRESERVE‐EF study, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analyzed.ResultsAmong the NIRFs examined, the presence of signal averaged ECG‐late potentials (SAECG‐LPs) ≥ 2/3 and non‐sustained ventricular tachycardia (NSVT) ≥1 eposode/24 h cutoff points were important predictors of a positive PVS study, demonstrating in the logistic regression analysis odds ratios 2.285 (p = .027) and 2.867 (p = .006), respectively. A simple risk score based on the above cutoff points in combination with LVEF < 50% presented high sensitivity but low specificity for a positive PVS.ConclusionCutoff points of NSVT ≥ 1 episode/24 h and SAECG‐LPs ≥ 2/3 in combination with a LVEF < 50% were important predictors of inducibility. However, the final decision for an ICD implantation should be based on a positive PVS, which is irreplaceable in risk stratification.     

Re‐adjudication of the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) with study‐level meta‐analysis of hospitalization for heart failure from cardiovascular outcomes trials with dipeptidyl peptidase‐4 (DPP‐4) inhibitors

BackgroundTrial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) assessed the cardiovascular (CV) safety of sitagliptin versus placebo on CV outcomes in patients with type 2 diabetes and CV disease and found sitagliptin noninferior to placebo. Subsequently, based on feedback from FDA, the Sponsor of the trial, Merck & Co., Inc., engaged a separate academic research organization, the TIMI Study Group, to re‐adjudicate a prespecified set of originally adjudicated events.MethodsTIMI adjudicated in a blinded fashion all potential hospitalization for heart failure (HHF) events, all potential MACE+ events previously adjudicated as not an endpoint event, and a random subset (~10%) of MACE+ events previously adjudicated as an endpoint event. An updated study‐level meta‐analysis of four randomized, placebo‐controlled, CV outcomes trials with dipeptidyl peptidase 4 (DPP‐4) inhibitors was then performed.ResultsAfter re‐adjudication of potential HHF events in the intent‐to‐treat population, there were 224 patients with a confirmed event in the sitagliptin arm (1.05/100 person‐years) and 239 patients in the placebo arm (1.13/100 person‐years), corresponding to a hazard ratio (HR) of 0.94 (95% confidence interval [95% CI]: 0.78–1.13, p = .49). Concordance between the outcome of the original adjudication and the re‐adjudication for HHF events was 82.7%. The meta‐analysis of CV outcomes trials with DPP‐4 inhibitors with placebo and involving 43 522 patients yielded an HR of 1.07 (95% CI: 0.83–1.39), with moderate heterogeneity (p = .45, I ² = 62.07%).ConclusionThe results of this independent re‐adjudication process and analyses of CV outcomes from TECOS were consistent with the original adjudication results and overall study findings. An updated study‐level meta‐analysis showed no overall significant risk for HHF with DPP‐4 inhibitors, but with statistical heterogeneity.