Metabolic cost of unloading pedalling in different groups of patients with pulmonary hypertension and volunteers.

Recently, the parameter internal work (IW) has been introduced as change in oxygen uptake (VO2) between resting and unloading workload in cardiopulmonary exercise testing (CPET). The proportional IW (PIW) was defined as IW divided by VO2 at peak exercise. A second option is to calculate the PIW based on the workload [PIW (Watt)] by considering the aerobic efficiency. The aim of our study was to investigate whether IW and PIW differ between patients with and without pulmonary hypertension and healthy controls. Our study population consisted of 580 patients and 354 healthy controls derived from the Study of Health in Pomerania. The PIW was slightly lower in patients (14.2%) than in healthy controls (14.9%; p = 0.030), but the PIW (Watt) was higher in patients (18.0%) than in the healthy controls (15.9%; p = 0.001). Such a difference was also observed, when considering only the submaximal workload up to the VAT (19.8% in patients and 15.1% in healthy controls; p < 0.001). Since the PIW (Watt) values were higher in patients with pulmonary hypertension, this marker may serve as a useful CPET parameter in clinical practice. In contrast to most of the currently used CPET parameters, the PIW does not require a maximal workload for the patient. Further studies are needed to validate the prognostic significance of the PIW.

Proportional Internal Work-a New Parameter of Exercise Testing in Study of Health in Pomerania (SHIP).

PURPOSE: Cardiopulmonary exercise testing usually requires a maximal exhaustive effort by the patient and is time consuming. The purpose of this study was to assess whether the cost to initiate exercise termed "proportional internal work" (PIW) was related to cardiovascular disease (CVD) risk factors, ventilatory parameters, and mortality. METHODS: We used data from population-based Study of Health in Pomerania. A total of 2829 (49.5% female) study participants with a median age of 52 (42-62) yr were included. Standardized questionnaires were used to assess CV risk factors. The cardiopulmonary exercise testing was performed using a modified Jones protocol. Regression models adjusted for sex and age were used to relate PIW with CVD risk factors and ventilatory parameters. The PIW was calculated by the following formula: (Oxygen uptake at rest - Oxygen uptake without load)/V˙ o2peak ) × 100. Cox regression analysis was used to relate PIW and all-cause mortality. RESULTS: We identified a nonlinear association between PIW and percent predicted V˙ o2peak . Women had a 2.96 (95% CI, 2.61-3.32) greater PIW than men. With each year of age and every point in body mass index, the PWI increased by 0.04 (95% CI, 0.03-0.05) and 0.16 (95% CI, 0.12-0.20), respectively. After adjustment for age, sex, smoking, and body mass index, a 1-point greater PIW was associated with a 5% higher risk to die (HR = 1.05; 95% CI, 1.01-1.07). CONCLUSIONS: The PIW is a new cardiopulmonary exercise testing parameter related to CVD risk and all-cause mortality. Future studies should assess the prognostic relevance of PIW for CVD prevention.

Subtotal occlusion of the right coronary artery by Cardioband and its successful intervention via retrograde approach. Interventional flashlight.

In recent years, transcatheter approaches have changed the therapy of valvular regurgitation. One of these new techniques is the Cardioband ® tricuspid valve reconstruction system (Edwards Lifesciences Corp., Irvine, CA, USA), which allows an adjustment of the ring size but may cause a temporary deformation or even occlusion of the right coronary artery (RCA) due to its close proximity. We report on a patient with symptomatic and subtotal occlusion of the RCA after Cardioband implantation. The distortion was so sharp-cornered that antegrade re-canalizations failed. Finally, the subtotal occlusion was re-opened via retrograde approach and this stent remained open in long-term follow-up. We think this complication should be known and considered when using the Cardioband system. Learning objective: Transcatheter reconstruction of the tricuspid valve by Cardioband ® can lead to subtotal occlusion of the right coronary artery, which is difficult to re-canalize.

Primary mitochondrial disease as a rare cause of unclear breathlessness and distinctive performance degradation - a case report.

BACKGROUND: Primary muscular disorders (metabolic myopathies, including mitochondrial disorders) are a rare cause of dyspnea. We report a case of dyspnea caused by a mitochondrial disorder with a pattern of clinical findings that can be classified in the known pathologies of mitochondrial deletion syndrome. CASE PRESENTATION: The patient presented to us at 29 years of age, having had tachycardia, dyspnea, and functional impairment since childhood. She had been diagnosed with bronchial asthma and mild left ventricular hypertrophy and treated accordingly, but her symptoms had worsened. After more than 20 years of progressive physical and social limitations was a mitochondrial disease suspected in the exercise testing. We performed cardiopulmonary exercise testing (CPET) with right heart catheterization showed typical signs of mitochondrial myopathy. Genetic testing confirmed the presence of a ~ 13 kb deletion in mitochondrial DNA from the muscle. The patient was treated with dietary supplements for 1 year. In the course of time, the patient gave birth to a healthy child, which is developing normally. CONCLUSION: CPET and lung function data over 5 years demonstrated stable disease. We conclude that CPET and lung function analysis should be used consistently to evaluate the cause of dyspnea and for long-term observation.

Prognostic Relevance of Cardiopulmonary Exercise Testing for Patients with Chronic Thromboembolic Pulmonary Hypertension.

Background: Following acute pulmonary embolism (PE), a relevant number of patients experience decreased exercise capacity which can be associated with disturbed pulmonary perfusion. Cardiopulmonary exercise testing (CPET) shows several patterns typical for disturbed pulmonary perfusion. Research question: We aimed to examine whether CPET can also provide prognostic information in chronic thromboembolic pulmonary hypertension (CTEPH). Study Design and Methods: We performed a multicenter retrospective chart review in Germany between 2002 and 2020. Patients with CTEPH were included if they had ≥6 months of follow-up and complete CPET and hemodynamic data. Symptom-limited CPET was performed using a cycle ergometer (ramp or Jones protocol). The association of anthropometric data, comorbidities, symptoms, lung function, and echocardiographic, hemodynamic, and CPET parameters with survival was examined. Mortality prediction models were calculated by Cox regression with backward selection. Results: 345 patients (1532 person-years) were included; 138 underwent surgical treatment (pulmonary endarterectomy or balloon pulmonary angioplasty) and 207 received only non-surgical treatment. During follow-up (median 3.5 years), 78 patients died. The death rate per 1000 person-years was 24.9 and 74.2 in the surgical and non-surgical groups, respectively (p < 0.001). In age- and sex-adjusted Cox regression analyses, CPET parameters including peak oxygen uptake (VO2peak, reflecting cardiopulmonary exercise capacity) were prognostic in the non-surgical group but not in the surgical group. In mortality prediction models, age, sex, VO2peak (% predicted), and carbon monoxide transfer coefficient (% predicted) showed significant prognostic relevance in both the overall cohort and the non-surgical group. In the non-surgical group, Kaplan−Meier analysis showed that patients with VO2peak below 53.4% predicted (threshold identified by receiver operating characteristic analysis) had increased mortality (p = 0.007). Interpretation: The additional measurement of cardiopulmonary exercise capacity by CPET allows a more precise prognostic evaluation in patients with CTEPH. CPET might therefore be helpful for risk-adapted treatment of CTEPH.

Comparison between thermodilution and Fick methods for resting and exercise-induced cardiac output measurement in patients with chronic dyspnea.

Studies comparing thermodilution (TD) and the direct Fick method (dFM) for cardiac output (CO) measurement are rare. We compared CO measurements between TD (2-5 cold water injections), the dFM, and indirect Fick method (iFM) at rest and during exercise, and assessed the effect of averaging different numbers of TD measurements during exercise. This retrospective study included 300 patients (52.3% women, mean age 66 ± 11 years) having pulmonary hypertension (76.0%) or unexplained dyspnea. Invasive hemodynamic and gas exchange parameters were measured at rest (supine; n = 300) and during unloaded cycling (semi-supine; n = 275) and 25-W exercise (semi-supine; n = 240). All three methods showed significant differences in CO measurement (ΔCO) at rest (p ≤ 0.001; ΔCO > 1 L/min: 45.0% [iFM vs. dFM], 42.0% [iFM vs. TD], and 45.7% [TD vs. dFM]). ΔCO (TD vs. dFM) was significant during unloaded cycling (p < 0.001; ΔCO > 1 L/min: 56.6%) but not during 25-W exercise (p = 0.137; ΔCO > 1 L/min: 52.8%). ΔCO (TD vs. dFM) during 25-W exercise was significant when using one or two (p ≤ 0.01) but not three (p = 0.06) TD measurements. Mean ΔCO (TD [≥3 measurements] vs. dFM) was -0.43 ± 1.98 and -0.06 ± 2.29 L/min during unloaded and 25-W exercise, respectively. Thus, TD and dFM CO measurements are comparable during 25-W exercise (averaging ≥3 TD measurements), but not during unloaded cycling or at rest. Individual ΔCOs vary substantially and require critical interpretation to avoid CO misclassification.

Correlation of Hemodynamic and Respiratory Parameters in Invasive Cardiopulmonary Exercise Testing (iCPET).

Background: Invasive cardiopulmonary exercise testing (iCPET) is an integral part in the advanced diagnostic workup of pulmonary hypertension (PH). Our study evaluated the relation between hemodynamic and respiratory parameters at two different resting conditions and two defined low exercise levels with a close synchronization of measurements in a broad variety of dyspnea patients. Subjects and methods: We included 146 patients (median age 69 years, range 22 to 85 years, n = 72 female) with dyspnea of uncertain origin. Invasive hemodynamic and gas exchange parameters were measured at rest, 45° upright position, unloaded cycling, 25 and 50 W exercise. All measurements were performed in a single RHC procedure. Results: Oxygen uptake (VO2/body mass) correlated significantly with cardiac index (all p ≤ 0.002) at every resting and exercise level and with every method of cardiac output measurement (thermodilution, method of Fick). Mean pulmonary arterial pressure (PAPmean) correlated with all respiratory parameters (respiratory rate, partial end-tidal pressures of oxygen and carbon dioxide [petCO2 and petO2], ventilation/carbon dioxide resp. oxygen ratio [VE/VCO2, VE/VO2], and minute ventilation [VE], all p < 0.05). These correlations improved with increasing exercise levels from rest via unloaded cycling to 25 W. There was no correlation with right atrial or pulmonary arterial wedge pressure. Summary: In dyspnea patients of different etiologies, the cardiac index is closely linked to VO2 at every level of rest and submaximal exercise. PAPmean is the only pressure that correlates with different respiratory parameters, but this correlation is highly significant and stable at rest, unloaded cycling and at 25 W.

[Invasive Cardiopulmonary Exercise Testing: A Review]. / Übersicht über die Entwicklung der invasiven Spiroergometrie (iCPET).

Right heart catheterization (RHC) is the internationally standardized reference method for measuring pulmonary hemodynamics under resting conditions. In recent years, increasing efforts have been made to establish the reliable assessment of exercise hemodynamics as well, in order to obtain additional diagnostic and prognostic data. Furthermore, cardiopulmonary exercise testing (CPET), as the most comprehensive non-invasive exercise test, is increasingly performed in combination with RHC providing detailed pathophysiological insights into the exercise response, so-called invasive cardiopulmonary exercise testing (iCPET).In this review, the accumulated experience with iCPET is presented and methodological details are discussed. This complex examination is especially helpful in differentiating the underlying causes of unexplained dyspnea. In particular, early forms of cardiac or pulmonary vascular dysfunction can be detected by integrated analysis of hemodynamic as well as ventilatory and gas exchange data. It is expected that with increasing validation of iCPET parameters, a more reliable differentiation of normal from pathological stress reactions will be possible.

Strategies for optimizing intravenous prostacyclin-analog therapy in patients with pulmonary arterial hypertension.

INTRODUCTION: Intravenous prostacyclin-analogs (PCA, e.g. epoprostenol, treprostinil, iloprost) have become an essential part in the therapy of patients with pulmonary hypertension (PH), mainly pulmonary arterial hypertension (PAH). They show considerable differences in pharmacology. A combination therapy including intravenous drugs is regarded as the 'gold standard' in most of PAH patients. AREAS COVERED: This review discusses and summarizes the studies and concepts on which this therapy is based. To date, intravenous prostacyclin-analogs are mainly administered when standard therapy fails to improve patients to low-risk status. However, preliminary data from uncontrolled studies suggest that an 'upfront triple' therapy including intravenous or subcutaneous prostacyclin-analogs could be preferable in selected patients. EXPERT OPINION: Various IV PCA have been evaluated in the treatment of patients with PAH. Today, combination therapy is the 'gold standard' for the majority of patients. Intravenous PCA is recommended from functional class III onwards. Timing of its initiation is still a point of discussion. An escalation of therapy to IV or SC PCA is always necessary if a low-risk status cannot be achieved with other targeted therapies. Preliminary data suggest that selected patients could benefit from an 'upfront triple' therapy. Controlled studies on which such recommendation could be based are lacking.

Inhalation of publicly available indoor insecticide spray caused myocardial infarction type II: a case report.

We report on a 70-year-old woman who tried to eliminate ants from her kitchen by applying a publicly available insecticide spray. Immediately afterwards, she felt dyspnoea, superseded by heavy chest pain. High-sensitivity troponin concentration increased from 33 to 149 ng/L (cut-off 50 ng/L). Significant coronary stenosis was excluded by coronary angiography, and the myocardial damage was classified as myocardial infarction type II. After exclusion of other potential mechanisms, we consider a cardiotoxic effect of the insecticide mixture of cypermethrin, tetramethrin, and piperonyl butoxide possible. We conclude that consumer information has to be improved. This concerns sustainable control measures adapted to the target insect species (in this case, the black garden ant Lasius niger), and differentiation between authorized and non-authorized but notified products. The instructions for use should give clear information on vulnerable groups and recommend personal protective equipment. Physicians and authorities should be alert to cardiac side-effects of insecticides.

Intravenous prostacyclin-analogue therapy in pulmonary arterial hypertension - A review of the past, present and future.

Therapy with intravenous prostacyclin analogues in patients with pulmonary arterial hypertension (PAH) has been established for decades and is an integral component of the current guidelines for the treatment of pulmonary hypertension. Initially, these drugs were infused by external pump systems via tunnelled right atrial catheters with the need for cooling and frequent exchange of drug reservoirs. Associated complications included, among others, catheter-related infections. More recently, fully implantable pump systems have been developed with drug reservoirs that are filled transcutaneously, allowing intervals between refills of several weeks. This technique results in a low rate of infections. Epoprostenol, iloprost and treprostinil have all been used intravenously in PAH, but titration, dosing and dose escalation in long-term therapy are not standardized. Intravenous prostacyclin analogues are still under-used, despite available data suggesting that early and broad application of these therapies as part of risk-oriented, guideline-directed combination therapy for patients with PAH may lead to a survival benefit. This review provides a detailed overview of the drugs, infusion systems and dosing strategies used for intravenous therapy in patients with PAH.

Ventricular fibrillation and Takotsubo cardiomyopathy triggered by media panic on COVID-19: A case report.

Takotsubo cardiomyopathy has potentially lethal complications and can be caused by a media-induced diffuse atmosphere of life threatening and panic in preconditioned patients.

Near fatal stent thrombosis in an aneurysmatic RCX as first manifestation of heparin induced thrombocytopenia (HIT) without thrombocytopenia.

BACKGROUND: Thrombosis resulting from heparin-induced thrombocytopenia (HIT) occurs in about 2% of patients without a significant decrease in platelet counts. We report on such a near fatal thrombotic event caused by coronary intervention. CASE PRESENTATION: A supposedly "completely healthy" 53-year-old patient was admitted to hospital with covered rupture of an aneurysm of the Aorta descendens. He was successfully operated on and underwent coronary angiography due to NSTEMI six days later. Immediately after intervention of a 90% RCX stenosis he developed ventricular flutter, was defibrillated, and re-angiography showed partial occlusion of the RCX stent. Lots of white thrombi could be retrieved by aspiration catheter and gave reason for a HIT without thrombocytopenia. The detection of platelet factor 4/heparin complex antibodies by immunoassay supported and the subsequent Heparin Induced Platelet Activation Assay proved this diagnosis. CONCLUSIONS: The clinical event of an acute stent thrombosis should alarm the interventional team to the diagnosis of HIT even with a normal platelet count.

Exercise and fluid challenge during right heart catheterisation for evaluation of dyspnoea.

This prospective study compared exercise test and intravenous fluid challenge in a single right heart catheter procedure to detect latent diastolic heart failure in patients with echocardiographic heart failure with preserved ejection function. We included 49 patients (73% female) with heart failure with preserved ejection function and pulmonary artery wedge pressure ≤15 mmHg. A subgroup of 26 patients had precapillary pulmonary hypertension. Invasive haemodynamic and gas exchange parameters were measured at rest, 45° upright position, during exercise, after complete haemodynamic and respiratory recovery in lying position, and after rapid infusion of 500 mL isotonic solution. Most haemodynamic parameters increased at both exercise and intravenous fluid challenge, with the higher increase at exercise. Pulmonary vascular resistance decreased by -0.21 wood units at exercise and -0.56 wood units at intravenous fluid challenge (p = 0.3); 20% (10 of 49) of patients had an increase in pulmonary artery wedge pressure above the upper limit of 20 mmHg at exercise, and 20% above the respective limit of 18 mmHg after intravenous fluid challenge. However, only three patients exceeded the upper limit of pulmonary artery wedge pressure in both tests, i.e. seven patients only at exercise and seven other patients only after intravenous fluid challenge. In the subgroup of pulmonary hypertension patients, only two patients exceeded pulmonary artery wedge pressure limits in both tests, further five patients at exercise and four patients after intravenous fluid challenge. A sequential protocol in the same patient showed a significantly higher increase in haemodynamic parameters at exercise compared to intravenous fluid challenge. Both methods can unmask diastolic dysfunction at right heart catheter procedure, but in different patient groups.

Prognostic value of cardiopulmonary exercise testing in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a severe rheumatic disease of the interstitial tissue, in which heart and lung involvement can lead to disease-specific mortality. Our study tests the hypothesis that in addition to established prognostic factors, cardiopulmonary exercise testing (CPET) parameters, particularly peak oxygen uptake (peakVO2) and ventilation/carbon dioxide (VE/VCO2)-slope, can predict survival in patients with SSc. SUBJECTS AND METHODS: We retrospectively assessed 210 patients (80.9% female) in 6 centres over 10 years with pulmonary testing and CPET. Survival was analysed with Cox regression analysis (adjusted for age and gender) by age, comorbidity (Charlson-Index), body weight, body-mass index, extensive interstitial lung disease, pulmonary artery pressure (measured by echocardiography and invasively), and haemodynamic, pulmonary and CPET parameters. RESULTS: Five- and ten-year survival of SSc patients was 93.8 and 86.9%, respectively. There was no difference in survival between patients with diffuse (dcSSc) and limited cutaneous manifestation (lcSSc; p = 0.3). Pulmonary and CPET parameters were significantly impaired. Prognosis was worst for patients with pulmonary hypertension (p = 0.007), 6-min walking distance < 413 m (p = 0.003), peakVO2 < 15.6 mL∙kg- 1∙min- 1, and VE/VCO2-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO2-slope (HR = 0.9; CI 0.82;0.98), diffusion capacity (Krogh factor, HR = 0.92; CI 0.86;0.98), forced vital capacity (FVC, HR = 0.91; CI 0.86;0.96), and peakVO2 (HR = 0.87; CI 0.81;0.94) were significantly linked to survival in multivariate analyses (Harrell's C = 0.95). This is the first large study with SSc patients that demonstrates the prognostic value of peakVO2 < 15.6 mL∙kg- 1∙min- 1 (< 64.5% of predicted peakVO2) and VE/VCO2-slope > 35.

Interobserver variability of ventilatory anaerobic threshold in asymptomatic volunteers.

BACKGROUND: The ventilatory anaerobic threshold (VO2@AT) has been used in preoperative risk assessment and rehabilitation for many years. Our aim was to determine the interobserver variability of AT using cardiopulmonary exercise (CPET) data from a large epidemiological study (SHIP, Study of Health in Pomerania). METHODS: VO2@AT was determined from CPET of 1,079 cross-sectional volunteers, according to American Heart Association guidelines. VO2@AT determinations were compared between two experienced physicians, between physicians and qualified medical assistants, and between physicians or medical assistants and software-based algorithms. For the first 522 data sets, the two physicians discussed discrepant readings to reach consensus; the remaining data sets were analyzed without consensus discussion. RESULTS: VO2@AT was detectable in 1,056 data sets. The physicians recorded identical VO2@AT values in 319 out of 522 cases before consensus discussion (61.1%; intraclass correlation coefficient [ICC]: 0.90; 95% confidence interval [CI]: 0.88-0.92) and in 700 out of 1,056 cases overall (66.3%; ICC: 0.95; 95% CI: 0.95-0.96), with an interobserver difference of 0 ± 8% (95% limits of agreement [LOA]: ±161 mL/min). The interobserver difference was - 2 ± 18% (95% LOA: ±418 mL/min) between a physician and medical assistants, and - 19 ± 24% to - 22 ± 26% (95% LOAs: ±719-806 mL/min) between physicians or medical assistants and software-based algorithms. CONCLUSIONS: Experienced physicians show high agreement when determining AT in asymptomatic volunteers. However, agreement between physicians and qualified medical assistants is lower, and there is substantial deviation in AT determination between physicians or medical assistants and software-based algorithms. This must be considered when using AT as a decision tool.

Predictive Capability of Cardiopulmonary and Exercise Parameters From Day 1 to 6 Months After Acute Pulmonary Embolism.

We hypothesized that the slope of relation ventilation to carbon dioxide output (V'E/V'CO2-slope) could be predictive already during the very first days after submassive pulmonary embolism (PE) to right ventricular systolic pressure (RVsys by echocardiography) after 6 months. We evaluated 21 hemodynamically stable patients at admittance, at days 3, 7, 90, and 180 by cardiopulmonary exercise testing and echocardiography. V'E/V'CO2-slope (48.4 ± 10.8) decreased within the first week (43.0 ± 9.8 at day 7) and normalized until follow-up at 6 months (35.0 ± 11.3; P < 10-4), p(a-ET)CO2 remained abnormal between days 1 and 3 (5.0 ± 3.9 to 6.7 ± 5.3 mmHg). RVsys declined from 41.7 ± 14.3 to 26.3±13.1 mmHg (P < 10-4) at 6 months. V'E/V'CO2-slope (r²= 0.27; P < .02) and RVsys (r² = 0.28; P = .03) at day 7 correlated with RVsys at 6 months. p(a-ET)CO2, p(a-ET)O2, V'D/V'T were not related to RVsys after 6 months. RVsys 6 months after acute PE is positively correlated with the V'E/V'CO2-slope at day 7.

Vasodilation and Exercise Capacity in Patients with End-Stage Renal Disease: A Prospective Proof-of-Concept Study.

BACKGROUND: Previous data have pointed to the fact that vascular function is significantly impaired in patients with end-stage renal disease (ESRD). We aimed to better characterise vasodilation and exercise capacity in both ESRD and chronic heart failure (CHF) patients. METHODS: A total of 30 ESRD patients (23 male; mean age 45.7 ± 9.9 years) were included in a prospective proof-of-concept study at a tertiary care academic centre. The patients underwent forearm venous plethysmography with post-ischaemic peak blood flow (PF) and flow-dependent flow (FDF) testing as well as cardiopulmonary exercise testing during the morning of the day following the last haemodialysis. After matching for age, gender, and body mass index, the data were compared to 30 patients with CHF and 20 age-matched healthy controls. RESULTS: PF in ESRD patients was reduced when compared to that in CHF patients (12.5 ± 4.2 vs. 15.6 ± 6.9 ml/100 ml/min; p = 0.048) and healthy controls (26.4 ± 9.3 ml/100 ml/min; p < 0.001). When compared to controls, FDF was significantly reduced in ESRD patients (7.6 ± 3.1 vs. 6.0 ± 2.5 ml/100 ml/min; p = 0.03), but not in CHF patients, whereas resting blood flow did not differ between the ESRD, CHF, and healthy control groups. In contrast to indices of vasodilative capacity, maximum exercise capacity (peakVO2) was higher in ESRD when compared to CHF patients (23.8 ± 7.3 vs. 18.8 ± 5.2 ml/min/kg), but significantly impaired when compared to controls (32.8 ± 6.7 ml/min/kg; p < 0.001). CONCLUSION: In this proof-of-concept study, exercise capacity was relatively preserved, while vasodilative capacity was substantially impaired in ESRD patients. Additional studies are warranted to examine the underlying mechanisms and potential clinical implications of our findings.

Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy.

AIMS: Previous studies showed unfavourable effects of right ventricular (RV) pacing. Ventricular pacing (VP), however, is required in many patients with atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV) remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced heart failure. The pre-specified PREVENT-HF German Substudy examined exercise capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). METHODS AND RESULTS: Patients with expected VP ≥80% were randomized to RV or BIV pacing. Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP. Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19), and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min, confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14 mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2 persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90). CONCLUSION: Our study suggests that BIV pacing produces better exercise capacity over 1 year compared with RV pacing in patients without advanced heart failure and AV block. In contrast, we observed no significant changes of NT-proBNP. Larger trials will allow appraising the clinical usefulness of BIV pacing in AV block. ClinicalTrials.gov Identifier: NCT00170326.