Novel Treatment Strategies for Right Heart Failure in Pulmonary Arterial Hypertension: Lessons from the Left Heart

Paulus, W.J. [Promotor]Vonk Noordegraaf, A. [Copromotor

Perspectives on novel therapeutic strategies for right heart failure in pulmonary arterial hypertension: lessons from the left heart

Right heart function is the main determinant of prognosis in pulmonary arterial hypertension (PAH). At present, no treatments are currently available that directly target the right ventricle, as we will demonstrate in this article. Meta-analysis of clinical trials in PAH revealed that current PAH medication seems to have limited cardiac-specific effects when analysed by the pump-function graph. Driven by the hypothesis that "left" and right heart failure might share important underlying pathophysiological mechanisms, we evaluated the clinical potential of left heart failure (LHF) therapies for PAH, based on currently available literature. As in LHF, the sympathetic nervous system and the renin–angiotension–aldosterone system are highly activated in PAH. From LHF we know that intervening in this process, e.g. by angiotensin-converting enzyme inhibition or β-blockade, is beneficial in the long run. Therefore, these medications could be also beneficial in PAH. Furthermore, the incidence of sudden cardiac death in PAH could be reduced by implantable cardioverter-defibrillators. Finally, pilot studies have demonstrated that interventricular dyssynchrony, present at end-stage PAH, responded favourably to cardiac resynchronisation therapy as well. In conclusion, therapies for LHF might be relevant for PAH. However, before they can be implemented in PAH management, safety and efficacy should be evaluated first in well-designed clinical trials

Diagnostic Accuracy of a Smartphone-Operated, Single-Lead Electrocardiography Device for Detection of Rhythm and Conduction Abnormalities in Primary Care

Contains fulltext : 209422.pdf (publisher's version ) (Closed access)PURPOSE: To validate a smartphone-operated, single-lead electrocardiography (1L-ECG) device (AliveCor KardiaMobile) with an integrated algorithm for atrial fibrillation (AF) against 12-lead ECG (12L-ECG) in a primary care population. METHODS: We recruited consecutive patients who underwent 12L-ECG for any nonacute indication. Patients held a smartphone with connected 1L-ECG while local personnel simultaneously performed 12L-ECG. All 1L-ECG recordings were assessed by blinded cardiologists as well as by the smartphone-integrated algorithm. The study cardiologists also assessed all 12L-recordings in random order as the reference standard. We determined the diagnostic accuracy of the 1L-ECG in detecting AF or atrial flutter (AFL) as well as any rhythm abnormality and any conduction abnormality with the simultaneously performed 12L-ECG as the reference standard. RESULTS: We included 214 patients from 10 Dutch general practices. Mean +/- SD age was 64.1 +/- 14.7 years, and 53.7% of the patients were male. The 12L-ECG diagnosed AF/AFL, any rhythm abnormality, and any conduction abnormality in 23, 44, and 28 patients, respectively. The 1L-ECG as assessed by cardiologists had a sensitivity and specificity for AF/AFL of 100% (95% CI, 85.2%-100%) and 100% (95% CI, 98.1%-100%). The AF detection algorithm had a sensitivity and specificity of 87.0% (95% CI, 66.4%-97.2%) and 97.9% (95% CI, 94.7%-99.4%). The 1L-ECG as assessed by cardiologists had a sensitivity and specificity for any rhythm abnormality of 90.9% (95% CI, 78.3%-97.5%) and 93.5% (95% CI, 88.7%-96.7%) and for any conduction abnormality of 46.4% (95% CI, 27.5%-66.1%) and 100% (95% CI, 98.0%-100%). CONCLUSIONS: In a primary care population, a smartphone-operated, 1L-ECG device showed excellent diagnostic accuracy for AF/AFL and good diagnostic accuracy for other rhythm abnormalities. The 1L-ECG device was less sensitive for conduction abnormalities