Andrew J. Sauer

Prognostic Importance of Pathophysiologic Markers in Patients With Heart Failure and Preserved Ejection Fraction

Background— Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome associated with multiple pathophysiologic abnormalities, including left ventricular (LV) diastolic dysfunction, longitudinal LV systolic dysfunction, abnormal ventricular-arterial coupling, pulmonary hypertension, and right ventricular (RV) remodeling/dysfunction. However, the relative prognostic significance of each of these pathophysiologic abnormalities in HFpEF is unknown. Methods and Results— We prospectively studied 419 patients with HFpEF using echocardiography and sphygmomanometry to assess HFpEF pathophysiologic markers. Cox proportional hazards analyses were used to determine the associations between pathophysiologic markers and outcomes. Mean age was 65±12 years; 62% were women; 39% were black; comorbidities were common; and study participants met published criteria for HFpEF. RV abnormalities were frequent: 28% had abnormal tricuspid annular plane systolic excursion, 15% had reduced RV fractional area change, and 34% had RV hypertrophy. During a median follow-up time of 18 months, 102 (24%) were hospitalized for HF and 175 (42%) experienced the composite end point of cardiovascular hospitalization or death. Decreased LV compliance, measured as reduced LV end-diastolic volume at an idealized LV end-diastolic pressure of 20 mm Hg (EDV20), and RV remodeling, as indicated by increased RV wall thickness, were the 2 pathophysiologic markers most predictive of worse outcomes: adjusted hazard ratio per 1 SD decrease in EDV20=1.39 (95% confidence interval [CI], 1.10–1.75; P=0.006), and hazard ratio per 1 SD increase in RV wall thickness=1.37 (95% CI, 1.16–1.61; P<0.001). These associations persisted after additional adjustment for markers of HF severity. By contrast, markers of LV relaxation, longitudinal LV systolic dysfunction, and ventricular-arterial coupling were not significantly associated with adverse outcomes. Conclusions— In patients with HFpEF, reduced LV compliance and RV remodeling are the strongest pathophysiologic predictors of adverse outcomes.

Clinical and Genetic Determinants of Torsade de Pointes Risk

Torsade de pointes (TdP) is a stereotyped polymorphic ventricular tachycardia characterized by a cyclic shifting of the QRS axis (twisting around the points of the isoelectric line) preceded by a prolonged QT interval (Figure 1). It is the quintessential arrhythmia of the long-QT syndrome (LQTS), whether congenital or acquired, and results from a complex interplay among structural, metabolic, genetic, and pharmacological determinants. Epidemiological risk factors such as sex, electrolyte imbalance, ischemia, and QT-prolonging drugs are well established. In this review, we explore the epidemiology, proposed mechanisms, ECG risk factors, and genetic architecture of TdP, particularly highlighting models for studying TdP and updating with potential clinical implications from recent genetic association studies of QT interval and sudden cardiac death (SCD). Figure 1. Telemetry strips demonstrating an example of torsade de pointes (TdP). In both strips, the top tracing represents lead II; the middle tracing, lead V1; and the bottom tracing, an arterial line waveform at the time of the arrhythmia. The stereotyped pattern of TdP is observed in which premature ventricular complexes, possibly caused by early afterdepolarizations, are followed by long R-R intervals setting up the short-long-short sequence that triggers polymorphic ventricular tachycardia. The arterial line confirms a pulseless cardiac arrest. The second rhythm strip shows the classic twisting morphology of the ventricular tachycardia that degenerates into ventricular fibrillation. The incidence of TdP is difficult to estimate because it can manifest as syncope or SCD without ECG documentation of the rhythm. US vital statistics recorded from 1989 to 1998 suggest that >300 000 lives are lost to SCD annually and that the proportion of SCD among cardiac causes of death has increased.1 As many as 80% of individuals dying suddenly are found to have coronary artery disease with acute or prior myocardial infarction, whereas 10% to 20% have no evidence …

Diastolic Electromechanical Coupling Association of the ECG T-Peak to T-End Interval With Echocardiographic Markers of Diastolic Dysfunction

Background— Electromechanical coupling, a well-described phenomenon in systolic dysfunction, has not been well studied in diastole. We hypothesized that the ECG T-peak to T-end (TpTe) interval, representing transmural dispersion of repolarization, is associated with echocardiographic markers of diastolic dysfunction (DD). Methods and Results— We performed a prospective, cross-sectional study of the association between TpTe and markers of DD in 84 consecutive, unselected patients referred for exercise echocardiography. We systematically measured TpTe on the resting ECG, and we performed comprehensive assessment of DD at rest and at peak stress. ECGs and echocardiograms were analyzed independently, blinded to each other and to all clinical data. By univariable analysis, increased TpTe was associated with older age, increased E/e’ ratio, and DD ( P <0.05 for all associations after correcting for multiple comparisons). Increased TpTe was inversely associated with reduced tissue Doppler e’ velocity, a marker of DD ( R = −0.66, P <0.0001). This association persisted after adjusting for age, QTc, exercise-induced wall motion abnormalities, and left ventricular mass index (β= −0.41 [95% confidence interval, −0.70 to −0.12] cm/s per 10-ms increase in TpTe; P =0.006). Baseline TpTe was also independently associated with resting DD (adjusted odds ratio, 3.9 [95% confidence interval, 1.4–10.7]; P =0.009) and peak exercise E/e’ ratio ( P <0.0001). Conclusions— Increased TpTe is associated with both resting and exercise-induced DD. Electromechanical coupling may represent a pathophysiologic link between electrical transmural dispersion of repolarization and abnormal myocardial relaxation, and may be a novel therapeutic target.Background—Electromechanical coupling, a well-described phenomenon in systolic dysfunction, has not been well studied in diastole. We hypothesized that the ECG T-peak to T-end (TpTe) interval, representing transmural dispersion of repolarization, is associated with echocardiographic markers of diastolic dysfunction (DD). Methods and Results—We performed a prospective, cross-sectional study of the association between TpTe and markers of DD in 84 consecutive, unselected patients referred for exercise echocardiography. We systematically measured TpTe on the resting ECG, and we performed comprehensive assessment of DD at rest and at peak stress. ECGs and echocardiograms were analyzed independently, blinded to each other and to all clinical data. By univariable analysis, increased TpTe was associated with older age, increased E/e’ ratio, and DD (P<0.05 for all associations after correcting for multiple comparisons). Increased TpTe was inversely associated with reduced tissue Doppler e’ velocity, a marker of DD (R= −0.66, P<0.0001). This association persisted after adjusting for age, QTc, exercise-induced wall motion abnormalities, and left ventricular mass index (&bgr;= −0.41 [95% confidence interval, −0.70 to −0.12] cm/s per 10-ms increase in TpTe; P=0.006). Baseline TpTe was also independently associated with resting DD (adjusted odds ratio, 3.9 [95% confidence interval, 1.4–10.7]; P=0.009) and peak exercise E/e’ ratio (P<0.0001). Conclusions—Increased TpTe is associated with both resting and exercise-induced DD. Electromechanical coupling may represent a pathophysiologic link between electrical transmural dispersion of repolarization and abnormal myocardial relaxation, and may be a novel therapeutic target.

Diastolic Electromechanical Coupling: Association of the Electrocardiographic T-peak to T-end Interval with Echocardiographic Markers of Diastolic Dysfunction

Background— Electromechanical coupling, a well-described phenomenon in systolic dysfunction, has not been well studied in diastole. We hypothesized that the ECG T-peak to T-end (TpTe) interval, representing transmural dispersion of repolarization, is associated with echocardiographic markers of diastolic dysfunction (DD). Methods and Results— We performed a prospective, cross-sectional study of the association between TpTe and markers of DD in 84 consecutive, unselected patients referred for exercise echocardiography. We systematically measured TpTe on the resting ECG, and we performed comprehensive assessment of DD at rest and at peak stress. ECGs and echocardiograms were analyzed independently, blinded to each other and to all clinical data. By univariable analysis, increased TpTe was associated with older age, increased E/e’ ratio, and DD ( P <0.05 for all associations after correcting for multiple comparisons). Increased TpTe was inversely associated with reduced tissue Doppler e’ velocity, a marker of DD ( R = −0.66, P <0.0001). This association persisted after adjusting for age, QTc, exercise-induced wall motion abnormalities, and left ventricular mass index (β= −0.41 [95% confidence interval, −0.70 to −0.12] cm/s per 10-ms increase in TpTe; P =0.006). Baseline TpTe was also independently associated with resting DD (adjusted odds ratio, 3.9 [95% confidence interval, 1.4–10.7]; P =0.009) and peak exercise E/e’ ratio ( P <0.0001). Conclusions— Increased TpTe is associated with both resting and exercise-induced DD. Electromechanical coupling may represent a pathophysiologic link between electrical transmural dispersion of repolarization and abnormal myocardial relaxation, and may be a novel therapeutic target.Background—Electromechanical coupling, a well-described phenomenon in systolic dysfunction, has not been well studied in diastole. We hypothesized that the ECG T-peak to T-end (TpTe) interval, representing transmural dispersion of repolarization, is associated with echocardiographic markers of diastolic dysfunction (DD). Methods and Results—We performed a prospective, cross-sectional study of the association between TpTe and markers of DD in 84 consecutive, unselected patients referred for exercise echocardiography. We systematically measured TpTe on the resting ECG, and we performed comprehensive assessment of DD at rest and at peak stress. ECGs and echocardiograms were analyzed independently, blinded to each other and to all clinical data. By univariable analysis, increased TpTe was associated with older age, increased E/e’ ratio, and DD (P<0.05 for all associations after correcting for multiple comparisons). Increased TpTe was inversely associated with reduced tissue Doppler e’ velocity, a marker of DD (R= −0.66, P<0.0001). This association persisted after adjusting for age, QTc, exercise-induced wall motion abnormalities, and left ventricular mass index (&bgr;= −0.41 [95% confidence interval, −0.70 to −0.12] cm/s per 10-ms increase in TpTe; P=0.006). Baseline TpTe was also independently associated with resting DD (adjusted odds ratio, 3.9 [95% confidence interval, 1.4–10.7]; P=0.009) and peak exercise E/e’ ratio (P<0.0001). Conclusions—Increased TpTe is associated with both resting and exercise-induced DD. Electromechanical coupling may represent a pathophysiologic link between electrical transmural dispersion of repolarization and abnormal myocardial relaxation, and may be a novel therapeutic target.

Echocardiographic markers of left ventricular unloading using a centrifugal-flow rotary pump

Echocardiographic markers of left ventricular unloading using a centrifugal-flow rotary pump Andrew J. Sauer, MD, Karen Meehan, ACNS-BC, Robert Gordon, MD, Travis Abicht, MD, Jonathan D. Rich, MD, Allen S. Anderson, MD, Clyde Yancy, MD, and Edwin C. McGee Jr, MD University Feinberg School of Medici Review Board. Once all baseline echocardiographic recorded, the speed was decreased every revolutions per minute (rpm) until the spee 2,200 to 2,400 rpm, which is the init determined by the speed that allowed f

Repolarization Heterogeneity: Beyond the QT Interval

Research over the past 2 decades has suggested that significant differences exist in the action potentials of endocardial, epicardial, and mid‐myocardial (M) cells that comprise the ventricular myocardium. Relative differences in the time course of repolarization of these 3 cell types, referred to

Echocardiography and Continuous-Flow Left Ventricular Assist Devices: Evidence and Limitations

Echocardiography is the most used imaging modality in the growing population of patients with advanced heart failure undergoing continuous-flow, durable mechanical circulatory support. However, no guidelines for the use of echocardiography in this population exist, evidence for core applications is limited and conflicting, and newer centrifugal-flow devices have been subject to minimal study. As a first step toward addressing these deficits, this review summarizes the evidence and expert opinion for the use of echocardiography in pre-operative planning and perioperative management, prediction of post-operative right ventricular failure, the use of echocardiographic surrogates for invasive hemodynamic measurements, and the performance of speed ramp studies for the diagnosis of thrombosis and optimization of device settings.

Electrocardiographic Markers of Repolarization Heterogeneity During Dofetilide or Sotalol Initiation for Paroxysmal Atrial Fibrillation

Serial electrocardiographic monitoring of ΔQTc as an assumed harbinger of proarrhythmia is currently recommended for dofetilide and sotalol initiation. Markers of repolarization heterogeneity such as increased peak to end of T-wave (TpTe) duration and abnormal T-wave morphology may also predict proarrhythmia. We investigated whether such T-wave measurements on baseline electrocardiogram will correlate with ΔQTc after drug initiation. An analysis of 140 consecutive patients with paroxysmal atrial fibrillation hospitalized in sinus rhythm for sotalol or dofetilide initiation was performed. Baseline and serial electrocardiograms were analyzed using QT Guard Plus software (GE Healthcare), which measured QTc and TpTe and scored T-wave morphology for asymmetry, notching, and flatness using T-wave vector magnitude and principal component analysis algorithms. Sotalol and dofetilide were administered in 71% and 29% of patients, respectively. Mean age was 61 ± 14 years, and 34% were women. After a single dose of either drug, there was a statistically significant increase in QTc and TpTe (p <0.01), as well as composite and individual T-wave markers of repolarization heterogeneity (p <0.01). QTc increased by a mean of 19 ± 30 ms after initial antiarrhythmic dose. ΔQTc was inversely related to baseline QTc and TpTe (p <0.01). After controlling for baseline QTc, there was no independent association between T-wave markers of repolarization heterogeneity and ΔQTc. In conclusion, for patients with paroxysmal atrial fibrillation admitted for dofetilide or sotalol loading, T-wave markers of increased repolarization heterogeneity are measurable within hours after initiation. A shorter baseline QTc is associated with an increased ΔQTc; however, there is no independent relation between baseline T-wave markers of repolarization heterogeneity and ΔQTc.

Endovascular repair of ventricular assist device outflow cannula stenosis

This report describes a case of endovascular repair of an outflow cannula obstruction in a heart failure patient with biventricular assist devices. The patient presented with cardiogenic shock and was diagnosed via multimodality imaging with outflow cannula obstruction of the left ventricular assist device, likely from a hematoma. A transesophageal echocardiogram‐guided endovascular approach was undertaken. A 10.0 mm × 38 mm covered stent was successfully deployed and post‐dilated. Normal flow in the outflow cannula was restored. Hemodynamic and left ventricular flow parameters returned close to baseline post‐procedure. The growth in ventricular assist device implantation and associated complications will create new opportunities for endovascular repair.

Percutaneous Closure of the Aortic Valve as a Bridge to Heart Transplantation to Treat Severe Aortic Insufficiency after Ventricular Assist Device

Aortic insufficiency (AI) following rotary left ventricular assist device (LVAD) implantation is an increasingly common problem with inadequately defined treatment options. Percutaneous transcatheter (PTC) closure of the aortic valve (AV) has been described as a potential nonsurgical approach. Alternatively, we present a case of decompensated heart failure due to de novo severe AI following LVAD in which successful PTC closure of the AV resolved the severe AI and allowed for clinical recovery and stability for more than 10 months as a bridge to heart transplantation.