Todd T. Schlegel

Open Access Integrated Therapeutic and Diagnostic Platforms for Personalized Cardiovascular Medicine

It is undeniable that the increasing costs in healthcare are a concern. Although technological advancements have been made in healthcare systems, the return on investment made by governments and payers has been poor. The current model of care is unsustainable and is due for an upgrade. In developed nations, a law of diminishing returns has been noted in population health standards, whilst in the developing world, westernized chronic illnesses, such as diabetes and cardiovascular disease have become emerging problems. The reasons for these trends are complex, multifactorial and not easily reversed. Personalized medicine has the potential to have a significant impact on these issues, but for it to be truly successful, interdisciplinary mass collaboration is required. We propose here a vision for open-access advanced analytics for personalized cardiac diagnostics using imaging, electrocardiography and genomics.

The prognostic value of positive T-wave in lead aVR in hemodialysis patients

BackgroundGiven that cardiac disease is the leading cause of mortality in hemodialysis (HD) patients, identification of patients at risk for cardiac mortality is crucial. The aim of this study was to determine if positive T-wave amplitude in lead aVR (TaVR) was predictive of cardiovascular (CV) mortality and sudden cardiac death (SCD) in a group of HD patients.Methods and resultsAfter exclusion, 223 HD patients were prospectively followed-up for 25.43xa0±xa03.56xa0months. Patients were divided into TaVR negative (nxa0=xa0186) and TaVR positive (nxa0=xa037) groups. Myocardial infarction, diabetes and beta-blocker therapy were more frequent in positive TaVR patients. Patients with upright TaVR were older, had higher left ventricular mass index, lower ejection fraction, higher calciumxa0×xa0phosphate product, higher troponin T level, higher prevalence of ST-T abnormalities, and increased width of QRS complex and QT interval, compared with patients with negative TaVR. A Kaplan–Meier analysis showed that the cumulative incidences of CV mortality as well as SCD were higher in patients with positive TaVR compared with those with negative TaVR (log-rank, pxa0<xa00.001 in both cases). A multivariate analysis selected age [hazard ratio (HR) 1.71, pxa0<xa00.001], heart rate (HR 1.42, pxa0=xa00.016), and positive TaVR (HR 2.21, pxa0=xa00.001) as well as age (HR 1.88, pxa0<xa00.001), and positive TaVR (HR 1.53, pxa0=xa00.014) as independent predictors of CV mortality and SCD, respectively.ConclusionIn HD patients, positive TaVR is an independent and powerful predictor of CV mortality as well as SCD. This simple ECG parameter provides additional information beyond what is available with other known traditional risk factors and allows the identification of patients most at risk of CV events.

Change in angular velocity at the end of the QRS loop aids the electrocardiographic detection of acute inferior myocardial infarction

We developed a new method for determining the QRS end, based on angular velocity (AV) changes around the QRS loop, and compared the methods performance to that of more established methods for determining QRS end in both healthy subjects and patients with acute myocardial infarction (AMI). Specifically, using Frank leads reconstructed from standard 12-lead ECGs, we determined AV in the direction of change raised to the 4th power, d(t). We found that the d(t)-determined AV transition (AVTr) nearly coincided with manually determined QRS end in healthy subjects, and in 27 patients with anterior AMI. However, in 31 patients with inferior AMI, AVTr typically preceded that of QRS end determined by the established methods, and by more than 10 ms in 32% of cases. While this “AVTr precedence” coincided with diagnostic ST elevation in only a minority of patients with recent inferior AMI, the use of AVTr precedence as a complement to more established methods for QRS end determination increased the sensitivity for detecting inferior AMIs from 23% to 42% without notably compromising specificity in healthy subjects (N=1050).

Intra-abdominal hypertension increases spatial QRS-T angle and elevates ST-segment J-point in healthy women undergoing laparoscopic surgery

BACKGROUNDnIntra-abdominal hypertension (IAH) impairs cardiovascular function, however an effect of IAH on cardiac electrophysiology has been poorly documented. The aim of this study was to evaluate the effect of IAH following pneumoperitoneum on vectorcardiographic variables reflecting cardiac repolarisation and depolarisation.nnnMETHODSnOtherwise healthy women undergoing elective gynaecological laparoscopy were studied. Intra-abdominal pressure (IAP), spatial QRS-T angle and ST-segment J-point (STJ) were observed during surgery and the early postoperative period.nnnRESULTSnForty women, ages 22 to 43 were examined. Induction of IAH to 15mmHg significantly widened the spatial QRS-T angle, whereas the Trendelenburg position subsequently reduced this widening. IAH also increased STJ voltage in leads III, aVF, V2 and V3 during surgery, with increased STJ voltage persisting in several leads through the morning of postoperative day 1.nnnCONCLUSIONnInduction of IAH impacts the relationship between cardiac depolarisation and repolarisation and increases spatial QRS-T angle and STJ voltage.

Spatial QRS-T angle in patients with newly diagnosed obstructive sleep apnea syndrome

PURPOSEnThe aim of the study was to assess the spatial QRS-T angle (QRS-TA) in a group of newly diagnosed and untreated adult patients with obstructive sleep apnea syndrome (OSAS) and to identify potential factors affecting this parameter.nnnPATIENTS AND METHODSnThe study group (PSG-confirmed OSAS) included 62 individuals, aged 51.7±10.3 years. The control group consisted of 25 individuals, aged 46.6±16.6 years with no sleep-disordered breathing. The diagnosis of OSAS and assessment of its severity was based on unattended all-night screening polysomnography. The spatial QRS-TA was reconstructed from 12-lead ECG using Kors regression method.nnnRESULTSnSignificant differences of spatial QRS-TA values were found between patients with severe OSAS (36.9±18.9°) and the controls (20.3±13.4°; p<0.01) and between patients with mild or moderate OSAS (32.3±20.1°) and the controls (p=0.01). Statistically significant correlations were found between spatial QRS-TA and polysomnographic indices (i.e. AHI, AI, RDT and RDTI).nnnCONLUSIONSnSpatial QRS-TA values are significantly higher in patients with OSAS than in controls, thus indicating increased heterogeneity of myocardial action potential. Further long-term prospective studies evaluating the prognostic value of spatial QRS-TA in OSAS patients are needed.

Changes in spatial QRS-T angle and QTc interval in patients with traumatic brain injury with or without intra-abdominal hypertension

IntroductionnTraumatic brain injury (TBI) affects cardiac electrical function, and several extra-cerebral factors, including intra-abdominal pressure (IAP), might further modulate this brain-heart interaction. The purpose of this study was to investigate the impact of TBI, and of increased IAP during TBI, on cardiac electrical function as measured by vectorcardiographic (VCG) variables.nnnMethodsnSurvival, IAP and changes in VCG variables including spatial QRS-T angle and QTc interval were measured in consecutive adult patients with either isolated TBI (iTBI), or with TBI accompanied by polytrauma to the abdomen and/or limbs (pTBI). For all patients, observations were performed just after the admission to the ICU (baseline) and at 24, 48, 72 and 96 h after admission.nnnResultsn74 patients aged 45 ± 18 were studied. 44 were treated for iTBI and 30 for pTBI. In all patients, spatial QRS-T angle and QTc interval increased after TBI (p < 0.001), relatively more so in patients with pTBI. Compared to survivors, non-survivors also ultimately had greater widening of the spatial QRS-T angle (p < 0.001), most notably just before foraminal herniation. Wider spatial QRS-T angle and longer QTc interval were also noted in patients with IAP > 12 mmHg (p < 0.001), and with right compared to left hemispheric injury (p < 0.001). ST segment level at the J point decreased 24 and 48 h after TBI in leads I, II, III, aVR, aVF, V1, V2, V3 and V6, and increased in lead V1, especially in non-survivors.nnnConclusionsnSpatial QRS-T angle and QTc interval increase after TBI. If foraminal herniation complicates TBI, further widening of the spatial QRS-T angle typically precedes it, followed by notable narrowing thereafter. Increased IAP also intensifies TBI-associated increases in spatial QRS-T angle and QTc interval.

Delineation of QRS offset by instantaneous changes in ECG vector angle can improve detection of acute inferior myocardial infarctions

We developed an automated new method for determining QRS offset, based on angular velocity (AV) changes around the QRS loop, and compared the methods performance to that of manual and more established automated methods for determining QRS offset in both healthy subjects and patients with acute myocardial infarction (AMI). Specifically, using Frank leads reconstructed from standard 12-lead ECGs, we determined AV in the direction of change raised to the 4th power, d(t). We found that the d(t)-determined AV transition (ΔAV) nearly coincided with manually determined QRS offset in healthy subjects, and in 27 patients with anterior AMI. However, in 31 patients with inferior AMI, ΔAV typically preceded that of QRS offset determined by the established automated methods, and by more than 10ms in 32% of cases. While this ΔAV precedence coincided with diagnostic ST elevation in only a minority of patients with recent inferior AMI, the use of ΔAV precedence as a complement to traditional determination of ST elevation increased the sensitivity for detecting inferior AMIs from 23 to 42%.

Personalized hypertension management in practice

The revolution occurring in genomic and personalized medicine is likely to have a significant impact on the management of hypertension. However, from the perspective of translating new knowledge into clinical practice, progress has been slow. This review article summarizes recent advances in hypertension-related diagnostics while also offering new perspective on hypertension management for the future. Such new perspectives will likely require a paradigm shift toward more integrated and holistic approaches for better prevention and treatment of hypertension in both individuals and the population as a whole.

High resolution ECG-aided early prognostic model for comatose survivors of out of hospital cardiac arrest

Out of hospital cardiac arrest (OHCA) has a high mortality despite modern treatment. Reliable early prognosis in OHCA could significantly improve clinical decision making. We explored prognostic utility of advanced ECG parameters, obtained from high-resolution ECG, in combination with clinical and OHCA-related parameters during treatment with mild induced hypothermia (MIH) and after rewarming in unconscious survivors of OHCA. Ninety-two patients during MIH and 66 after rewarming were included. During MIH, a score based on initial rhythm, QRS-upslope and systolic pressure resulted in an area under curve (AUC) of 0.82 and accuracy of 80% for survival. After rewarming, a score based on admission rhythm, sum of 12 lead QRS voltages, and mean lateral ST segment level in leads I and V6 resulted in an AUC of 0.88 and accuracy of 85% for survival. ECG can assist with early prognostication in unconscious survivors of OHCA during MIH and after rewarming.