First in human: the effects of biventricular pacing on cardiac output in severe pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) carries high morbidity and mortality despite available treatment options. In severe PAH, right ventricular (RV) diastolic pressure overload leads to interventricular septal bowing, hindering of left ventricular diastolic filling and reduced cardiac output (CO). Some animal studies suggest that pacing may mitigate this effect. We hypothesized that eliminating late diastole via ventricular pacing could improve CO in human subjects with severe PAH. Using minimal to no sedation, we performed transvenous acute biventricular (BiV) pacing and right heart catheterization in six patients with symptomatic PAH. Hemodynamic measurements were taken at baseline and during BiV pacing at various 20-ms intervals of V-V timing. We compared baseline CO to (1) CO while pacing the RV first by 80 ms (mimicking RV-only pacing), and then to (2) CO during pacing at the V-V timing that resulted in the highest CO. All participants were female, PASP 74 ± 14 mmHg, QRS duration 104 ± 20 ms. Compared with baseline, the CO decreased when the RV was paced first by 80 ms (7.2 ± 1.0 vs. 6.2 ± 1.1 L/min, p = 0.028). Pacing with optimal V-V timing produced CO similar to baseline (7.2 ± 1.0 vs. 7.4 ± 1.4, p = 0.92). Two patients (33%) met the predefined endpoint of a 15% increase in CO during pacing at the optimal V-V timing. In symptomatic PAH, V-V optimized acute BiV pacing does not consistently improve CO. However, acute BiV pacing did improve CO in a subset of this cohort. Further research is needed to identify predictors of response to cardiac resynchronization therapy in this population.

Relationships between the T-peak to T-end interval, ventricular tachyarrhythmia, and death in left ventricular systolic dysfunction.

AIMS: The interval between the T-wave's peak and end (Tpe), an electrocardiographic (ECG) index of ventricular repolarization, has been proposed as an indicator of arrhythmic risk. We aimed to clarify the clinical usefulness of Tpe for risk stratification. METHODS AND RESULTS: We evaluated 327 patients with left ventricular ejection fraction (LVEF) ≤ 35% (75% male, LVEF 23 ± 7%). All patients had an implanted implantable cardioverter-defibrillator (ICD). Clinical data and ECGs were analysed at baseline. Prospective follow-up for the endpoints of appropriate ICD therapy and mortality was conducted via periodic device interrogation, chart review, and the Social Security Death Index. During device clinic follow-up of 17 ± 12 months, 59 (18%) patients had appropriate ICD therapy, and during mortality follow-up of 30 ± 13 months, 67 (21%) patients died. A longer Tpe(c) predicted appropriate ICD therapy, death, and the combination of appropriate ICD therapy or death (P< 0.01 for each endpoint). On multivariable analysis correcting for other univariable predictors, Tpe(c) remained predictive of ICD therapy [hazard ratio (HR) per 10 ms increase: 1.16, P= 0.02], all-cause mortality (HR per 10 ms: 1.14, P= 0.03), and the composite endpoint of ICD therapy or death (HR per 10 ms: 1.16, P< 0.01). CONCLUSIONS: In patients with left ventricular systolic dysfunction and an implanted ICD, Tpe(c) independently predicts both ventricular tachyarrhythmia and overall mortality.

Device therapy for heart failure: when and for whom?

Surgical approaches to heart failure (HF) management have become a necessary strategy in response to a waiting list that is expanding in the face of a limited supply of organ donors. Multiple studies have supported the safety and efficacy of device-based therapy. Among the device-based therapy options, ventricular assist devices (VADs) represent an alternative to heart transplantation with the capability to function as short-term support, bridge-to-transplantation or recovery and as long-term support. VAD support may be considered in those with refractory cardiogenic shock or those with decompensated chronic HF that is unresponsive to maximized medical therapy. Composite scoring scales may be used to risk-stratify patients using clinical and laboratory values to allow more systematic patient selection. As the pursuit for a perfect device continues, so does the search for the best objective index to guide referral. Technologic advances will enhance device performance and extend VAD use into community practice. This discussion aims to highlight criteria for candidate selection and referral for VAD implantation.