Cor Allaart

Interventricular Mechanical Asynchrony in Pulmonary Arterial Hypertension Left-to-Right Delay in Peak Shortening Is Related to Right Ventricular Overload and Left Ventricular Underfilling

OBJECTIVES The purpose of this study was to explore in pulmonary arterial hypertension (PAH) whether the cause of interventricular asynchrony lies in onset of shortening or duration of shortening. BACKGROUND In PAH, leftward ventricular septal bowing (LVSB) is probably caused by a left-to-right (L-R) delay in myocardial shortening. METHODS In 21 PAH patients (mean pulmonary arterial pressure 55 +/- 13 mm Hg and electrocardiogram-QRS width 100 +/- 16 ms), magnetic resonance imaging myocardial tagging (14 ms temporal resolution) was applied. For the left ventricular (LV) free wall, septum, and right ventricular (RV) free wall, the onset time (T(onset)) and peak time (T(peak)) of circumferential shortening were calculated. The RV wall tension was estimated by the Laplace law. RESULTS The T(onset) was 51 +/- 23 ms, 65 +/- 4 ms, and 52 +/- 22 ms for LV, septum, and RV, respectively. The T(peak) was 293 +/- 58 ms, 267 +/- 22 ms, and 387 +/- 50 ms for LV, septum, and RV, respectively. Maximum LVSB was at 395 +/- 45 ms, coinciding with septal overstretch and RV T(peak). The L-R delay in T(onset) was -1 +/- 16 ms (p = 0.84), and the L-R delay in T(peak) was 94 +/- 41 ms (p < 0.001). The L-R delay in T(peak) was not related to the QRS width but was associated with RV wall tension (p < 0.05). The L-R delay in T(peak) correlated with leftward septal curvature (p < 0.05) and correlated negatively with LV end-diastolic volume (p < 0.05) and stroke volume (p < 0.05). CONCLUSIONS In PAH, the L-R delay in myocardial peak shortening is caused by lengthening of the duration of RV shortening. This L-R delay is related to LVSB, decreased LV filling, and decreased stroke volume.

Assessment of Intraventricular Mechanical Dyssynchrony and Prediction of Response to Cardiac Resynchronization Therapy: Comparison between Tissue Doppler Imaging and Real-Time Three-Dimensional Echocardiography

OBJECTIVE We studied the comparability of left ventricular (LV) mechanical dyssynchrony assessment by tissue Doppler imaging (TDI) and real-time three-dimensional echocardiography (RT3DE) in patients with a wide range of LV ejection fractions and different causes of cardiomyopathy. In addition, we evaluated the ability of both techniques to predict response to cardiac resynchronization therapy (CRT). METHODS A total of 90 patients and 30 healthy volunteers underwent both TDI and RT3DE. A subgroup of 27 patients underwent CRT and were evaluated before and 6 months after implantation. Mechanical dyssynchrony was measured with TDI using the standard deviation of time to peak systolic tissue velocity of 12 LV myocardial segments. With RT3DE, the standard deviation of time from QRS onset to minimal volume of 16 LV subvolumes was assessed. Indicators of response to CRT were a clinical improvement of >or= 1 New York Heart Association functional class, and reverse remodeling defined as a reduction of >or= 15% in LV end-systolic volume at 6 months. RESULTS A moderate correlation (r = 0.581, P < .001) was observed between TDI and RT3DE. No significant difference in the presence of mechanical dyssynchrony by TDI and RT3DE was observed (53% vs 48%, respectively). Agreement between techniques was comparable between patients with ischemic and nonischemic cardiomyopathy. However, up to 30% nonagreement between the 2 techniques was found, depending on the severity of LV dysfunction. Of the 27 patients undergoing CRT, clinical response was observed in 70% of patients, whereas reverse remodeling occurred in 63% of patients. All baseline characteristics were similar between responders and nonresponders, except for mechanical dyssynchrony assessed by RT3DE, which was significantly higher in responders compared with nonresponders (10.1% +/- 2.6% vs 5.1% +/- 1.2% for clinical response, P < .001; 10.0% +/- 2.8% vs 6.3% +/- 2.3% for reverse remodeling, P = .001). By applying previously defined cutoff values, receiver operating characteristic curve analysis demonstrated a sensitivity of 58% with a specificity of 50% for TDI and a sensitivity of 95% with a specificity of 87% for RT3DE to predict clinical response to CRT. For prediction of reverse remodeling after CRT, sensitivity and specificity were 59% and 50% for TDI, and 88% and 60% for RT3DE, respectively. The optimal cutoff value for systolic dyssynchrony index by RT3DE of 6.7% yielded a sensitivity of 90% with a specificity of 87% to predict clinical response, and a sensitivity of 88% with a specificity of 70% to predict reverse remodeling. CONCLUSION Marked differences between techniques are found for the presence of mechanical dyssynchrony when current cutoff values are applied, making interchangeability of these techniques uncertain. Assessment of mechanical dyssynchrony by RT3DE might be an appropriate alternative to TDI for accurate prediction of response to CRT.

Renal denervation in heart failure with normal left ventricular ejection fraction. Rationale and design of the DIASTOLE (DenervatIon of the renAl Sympathetic nerves in hearT failure with nOrmal Lv Ejection fraction) trial

Increasing evidence suggests an important role for hyperactivation of the sympathetic nervous system (SNS) in the clinical phenomena of heart failure with normal LVEF (HFNEF) and hypertension. Moreover, the level of renal sympathetic activation is directly related to the severity of heart failure. Since percutaneous renal denervation (pRDN) has been shown to be effective in modulating elevated SNS activity in patients with hypertension, it can be hypothesized that pRDN has a positive effect on HFNEF. The DIASTOLE trial will investigate whether renal sympathetic denervation influences parameters of HFNEF.

Stroke work or systolic dP/dtmax to evaluate acute response to cardiac resynchronization therapy: are they interchangeable?

Cardiac resynchronization therapy (CRT) is characterized by a ~30% non‐response. Invasive haemodynamic measurements are a traditional method to evaluate response to CRT. This study evaluates the correlation between acute changes in dP/dtmax and Stroke Work (SW) during CRT.

Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine

Abstract Background: Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For this purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine plasma-concentrations. We used two compartments with first order absorption. Case details: The maximum concentration of ibogaine was 1.45 mg/L. Our patient developed markedly prolonged QTc interval of 647ms maximum, several multiple cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and Torsades des Pointes). QTc-prolongation remained present until 12 days after ingestion, several days after ibogaine plasma-levels were low, implicating clinically relevant noribogaine concentrations long after ibogaine had been cleared from the plasma. The ratio k12/k21 for noribogaine was 21.5 and 4.28 for ibogaine, implicating a lower distribution of noribogaine from the peripheral compartment into the central compartment compared to ibogaine. Conclusions: We demonstrated a linear relationship between the concentration of the metabolite and long duration of action, rather than with parent ibogaine. Therefore, after (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due to its metabolite.

A protocol to screen patients with congestive heart failure for cardiac resynchronisation therapy by a nurse practitioner in an out- patient heart failure clinic

}SUMMARY In this article the negative effects and prognosis of a prolonged QRS •� duration in patients with congestive heart failure are discussed. The purpose, criteria for, and effects of cardiac resynchronisation •� therapy are described. A selection protocol for patients with congestive heart failure is •� outlined, with emphasis on the role of the Heart Failure Nurse Practitioner. Results of the selection protocol are presented.