Potential prevention of pacing-induced heart failure using simple pacemaker programming algorithm.

INTRODUCTION: Right ventricular pacing (RVP) causes ventricular desynchronization and may lead to the development of heart failure (HF). Prolongation of atrioventricular delay (AVD) in DDDR pacemakers reduces unnecessary RV stimulation. The aim of the study was to verify the influence of RVP reduction on HF symptoms. METHODS: The study comprised 31 patients (17 men, mean age: 71.6 ± 8 yrs) with DDDR pacemaker implanted due to sinus node dysfunction (SND). At baseline, 28 patients did not present any symptoms of HF. Three patients were in NYHA class II. Patients were randomized either to 150 ms AVD or to minimizing right ventricular pacing (MRVP). Crossing over to the alternate mode took place after 4 months. Cardiopulmonary exercise test (CPX), echocardiography (ECHO) and BNP measurements were done before pacemaker implantation, after 4 and 8 months. RESULTS: The percentage of RVP was significantly higher in 150 ms AVD than in MRVP: 81.7 ± 22.6 versus 14.2±20.5%, P < 0.0001. Patients with 150 ms mode had worse CPX parameters than those with MRVP mode: peak oxygen uptake was 14.2±4.3 versus 19.9±6.3 ml/kg per min, P = 0.0001, higher BNP concentrations: 72.3±48.3 versus 49.4±43.9 pg/ml, P = 0.001 and worse left ventricle [LV] function: ejection fraction: 53.2±6.7 versus 57.3±5.5%, P < 0.0001; LV diastolic diameter: 4.86±0.52 versus 4.66±0.5 cm, P < 0.01. CONCLUSION: Predominant RVP in patients without symptoms of HF at baseline may be responsible for worse performance in cardiopulmonary exercise test, higher BNP concentrations and impairment of LV function. Specific DDDR pacemaker programming promotes intrinsic AV conduction and may prevent the development of pacing-induced HF.

Impact of cardiac resynchronisation therapy on adaptation of circulatory and respiratory systems to exercise assessed by cardiopulmonary exercise test in patients with chronic heart failure.

BACKGROUND: Cardiac resynchronisation therapy (CRT) has become a valuable therapeutic tool in patients with advanced chronic heart failure (CHF). The search for optimal methods for the assessment of CRT efficacy is still underway. AIM: To evaluate the impact of implantation of CRT devices in patients with CHF on adaptation of circulatory and respiratory systems to maximal exercise assessed by cardiopulmonary exercise tests (CPX) and 6-minute walking tests (6MWT). METHODS: We investigated 27 patients (22 males, 5 females, 61.2+/-9.1 years) with a CRT device implanted due to advanced CHF, which resulted from ischaemic or dilated cardiomyopathy. All patients before implantation underwent echocardiography, CPX with expired gas analysis and 6MWT. Investigations were repeated at 3-6 months after CRT implantation. In CPX we evaluated peak oxygen uptake (peak VO2), oxygen pulse, maximal minute ventilation-carbon dioxide production (VE/VCO2 (max)), and its slope (VE/VCO2 slope) and VE/VO2 slope, VO2 in anaerobic threshold (AT), and cardiac and respiratory reserve. In 6MWT we evaluated walking distance and heart rate and blood pressure response to exercise. RESULTS: We noted statistically higher mean peak VO2 after CRT implantation in the studied group: 11.34+/-3.38 vs. 14.56+/-3.99 ml/kg/min (p<0.0001) and 1.01 +/-0.44 vs. 1.4+/-0.55 l/min (p=0.003) and higher values of expired CO2: 1.00+/-0.43 vs. 1.43+/-0.67 l/min (p=0.004). The O2 pulse rose from 9.65+/-3.39 to 13.23+/-5.43 ml/beat (p=0.015). We also observed a significant reduction of VE/VCO2 slope from 42.34+/-13.35 before CRT to 34.77+/-6.04 after CRT (p=0.0196) and a significant decrease of VE/VO2 slope from 41.32 +/-15.46 to 34.01+/-6.27 (p=0.037). VE/VCO2 (max) fell from 58.02+/-15.86 to 50.1+/-13.14 (p=0.009). Patients estimated their dyspnoea on the Borg scale at peak exercise at 4.75+/-0.75 points before CRT and at 3.67+/-1.15 points (p=0.002) after CRT. Patients could walk a longer distance during 6MWT than before CRT (367+/-154.9 vs. 231.1+/-170.3 m, p<0.001). CONCLUSIONS: Cardiac resynchronisation therapy improves exercise tolerance measured by means of CPX and 6MWT, improves respiratory system efficiency and restores its adaptive mechanisms during exercise in patients with advanced CHF. Better exercise adaptation after CRT may be objectively measured with CPX parameters, and correlates with improvement of clinical symptoms. CPX seems to be a very helpful tool in assessing the results of CRT.

[Clinical evaluation of pentaerythritol tetranitrate in two doses in patients with stable angina pectoris]. / Badania kliniczne czteroazotanu pentaerytrytylu w dwóch dawkach u pacjentów ze stabilna choroba wiencowa.

Pentaerythritol tetranitrate (PETN) has raised a great deal of interest in recent years, because it is probably the only organic "tolerance-sparing" nitrate. However, some clinicians doubt whether this drug is really effective in reducing angina and ischemia. The aim of this study, therefore, was to evaluate the clinical efficacy and adverse effects (AEs) of PETN in two doses: 50 mg (PETN-50) and 100 mg (PETN-100), after single ingestion. Twenty-five male patients (pts) with stable angina were enrolled in a randomized, double-blind and placebo (P) controlled study. Ten of them received PETN-50 or P and fifteen of them PETN-100 or P. Antianginal efficacy of the drugs was evaluated by analyzing the parameters of tolerance of effort and coronary reserve taken from serial exercise stress tests on the treadmill performed before single oral ingestion, then after 2h and 6h. Simple hemodynamic parameters were also evaluated at rest and during exercise. In comparison to P, PETN-50 did not change any parameter of tolerance of effort and coronary reserve, nor any simple hemodynamic parameter (all values statistically not significant - n.s.). However, in comparison to P, PETN-100 significantly improved the mean total walking time after 2h by 20.8% (p < 0.01) and also after 6h by 11.3% (p < 0.05). Similarly, PETN-100 improved walking time to angina after 2h by 18.8% (p < 0.05) and after 6h by 10.5% (p < 0.05). The drug also improved walking time to ischemia after 2h by 32.5% (p < 0.01) and after 6h by 13.8% (p < 0.05). PETN-100 did not significantly change the resting heart rate, but it decreased resting systolic blood pressure in both positions 6h after ingestion: in supine by 6.1% (p < 0.05) and in standing by 5.9% (p < 0.05). No postural hypotension in any pt occurred. Diastolic blood pressure significantly decreased only in standing position by 6.8% (p < 0.05) after 6h. During maximal exercise no significant reduction of systolic blood pressure occurred, but there was a significant reduction in diastolic blood pressure 6h after ingestion only. This study shows the good clinical tolerance and safety of PETN in both doses. There were no AEs after single ingestion of PETN-50 and AEs after ingestion of PETN-100 included headaches in 3 pts only (in 1 pt after P) in the group of 15 pts. Thus no clinical activity of PETN-50 was shown. However, our investigations suggest that PETN-100 is an active coronary drug, effective not less than 6 h after ingestion, and well tolerated by pts. Further studies are needed to evaluate the efficacy of PETN in long-term therapy.

Prognostic importance of the extent of coronary revascularisation in patients with acute coronary syndromes and multivessel disease: one-year prospective follow-up.

BACKGROUND: Interventional treatment improves prognosis in patients with acute coronary syndromes (ACS). However, despite introduction of percutaneous coronary intervention (PCI), the risk of cardiovascular events in patients with multivessel coronary artery disease (MVD) remains significant. AIM: To evaluate the risk of complications and the prognostic value of MVD in patients with ACS during 1-year follow-up. METHODS: A group of 153 patients with ACS was followed up at a single cardiology unit with round-the-clock PCI capability. Treatment of ACS, the extent of revascularisation, and complications occurring during hospitalisation and 1-year follow-up were analysed. The end points of the study were defined as death from all causes, cardiac death, recurrent ACS and a composite end point (deaths from cardiac causes and recurrent ACS). RESULTS: During 1-year follow-up, 11 (7.2%) patients died, including 10 patients with MVD without complete revascularisation. Recurrent ACS occurred in 18 (12%) patients, including 13 patients with MVD without complete revascularisation. Presence of a residual significant coronary stenosis in incompletely revascularised patients with MVD was an important risk factor for all-cause mortality and occurrence of a composite endpoint in comparison to MVD patients who underwent complete revascularisation (p = 0.028 and p = 0.046, respectively) and patients with single-vessel disease (p = 0.006 and p = 0.003, respectively). CONCLUSIONS: Incomplete revascularisation during the acute phase of ACS was associated with an increased risk of complications and a significantly increased risk of all-cause mortality and the combined rate of cardiovascular deaths and recurrent ACS. Single-stage PCI of all significant stenoses in MVD patients resulted in better outcomes.

[Development of nitrate tolerance in individual patients with stable angina pectoris in various phases of therapy with oral isosorbide dinitrate]. / Wystepowanie tolerancji azotanów u poszczególnych chorych ze stabilna dlawica piersiowa w róznych odmianach leczenia doustnym dwuazotanem izosorbitolu.

The aim of the work was an individual assessment of the effect on coronary reserve exerted by the widely used drug from the group of nitrates--isosorbide dinitrate (ISDN) in conventional and slow-release (SR) presentations, in various doses. The patients--38 males with stable coronary disease were given orally, by randomised double blind method, conventional isosorbide dinitrate (ISDN) in 10 and 20 mg doses, and slow-release isosorbide dinitrate in 20 mg SR, 40 mg SR, 80 mg SR and 120 mg SR doses, or placebo for the first time and for 7 days: four times daily, three times daily (with a 12-hour break), twice daily (with an 18-hour break) and once daily. In each of the therapeutic methods, walking times were analysed during exercise test six hours following drug administration, that is total time (TT), time to angina (TA) and time to ischaemia (TI). A prolongation by > or = 20% of walking times after ISDN administration as compared to placebo in > 50% of patients was accepted as significant improvement. Six hours after the first administration, a significant improvement of TT, TA and TI as compared to placebo was observed in the case of ISDN 20 mg, 40 mg SR, 80 mg SR and 120 mg SR. After administration of the drugs four times daily no significant improvement was observed after any dose. After administration of the drugs thrice daily, significant improvement was found in the case of TA (80 mg SR) and TI (20 mg SR, 40 mg SR and 120 mg SR), after twice daily administration--in the case of TI (40 mg SR and 80 mg SR) and after once daily administration--in the case of TT (80 mg SR), TA (120 mg SR) and TI (40 mg SR, 80 mg SR and 120 mg SR). In > 50% of patients, the coronary activity of ISDN in higher doses persists for six hours in the case of the first time administration; continuous therapy leads to tolerance development and intermittent therapy makes possible to avoid it. Tolerance does not depend on patients' sensitivity to nitrates.

[Clinical usefulness of high-dose oral nitroglycerin in patients with stable angina pectoris]. / Przydatnosc kliniczna nitrogliceryny w wysokiej dawce doustnej u chorych ze stabilna dlawica piersiowa.

The aim of this study was to evaluate clinical efficacy and adverse effects of nitroglycerin 15 mg in slow-release form (N-15) after single ingestion. In randomized, double-blind and placebo (P) controlled with cross-over design study 15 male patients with stable angina received N-15 or P. Antianginal efficacy of the drug was evaluated by analysing the parameters of tolerance of effort and coronary reserve taken from serial exercise stress tests on treadmill performed preceding single oral ingestion, 2 hours and 6 hours after. Simple hemodynamic parameters were also evaluated in the rest and during exercise. N-15 significantly improved in comparison to P: total walking time both after 2 hours by 34.3% (p < 0.01) and 6 hours by 23.1% (p < 0.01); walking time to angina after 2 hours by 34.8% (p < 0.01) and 6 hours by 21.7% (p < 0.05), and walking time to ischemia after 2 hours by 66.1% (p < 0.01) and 6 hours by 39.0% (p < 0.05). N-15 significantly increased the rest heart rate in standing position 2 hours after ingestion by 12.3% (p < 0.01) and decreased rest systolic blood pressure in both positions 2 hours after ingestion: in supine by 12.9% (p < 0.01) and standing by 16.3% (p < 0.01) and after 6 hours: in supine by 9.1% (p < 0.05) and standing by 10.0% (p < 0.05). No postural hypotension in any patient occurred. Diastolic blood pressure was significantly decreased only in standing position 2 hours after N-15 ingestion by 12.3% (p < 0.01) and after 6 hours by 9.1% (p < 0.05). During maximal exercise significant reduction of systolic blood pressure occurred 2 hours after ingestion and significant reduction of diastolic blood pressure occurred both 2 hours and 6 hours after ingestion. Adverse effects after single ingestion of N-15 were the few: the headaches were presented only in 4 patients (27%), and in 53% patients any adverse effect occurred. Nitroglycerin 15 mg in slow-release form is an active coronary drug, effective not less than 6 hours after ingestion, and its adverse effects are the few.

Long-term use of short- and long-acting nitrates in stable angina pectoris.

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

Anti-ischaemic response to sublingual nitroglycerin during oral administration of isosorbide dinitrate in patients with stable angina pectoris: when does cross-tolerance occur?

The purpose of this study was to evaluate the efficacy of sublingual nitroglycerin (NTG) during treatment with oral sustained-release isosorbide dinitrate (ISDN) in two doses: 80 mg and 120 mg. In a double-blind crossover design study 38 men with stable angina initially received either an oral placebo (OP) or ISDN. All patients received either NTG 0.5 mg or sublingual placebo (SLP) 2.5 h after OP ingestion, but only NTG 2.5 h after ISDN. The same pattern was used in the first ingestion and in long-term OP or ISDN therapy for 7 days (OP and ISDN every 6 h, and ISDN once daily). The efficacy of NTG was evaluated by analyzing walking time to ischaemia (WTI) during exercise tests performed 5 minutes after NTG or SLP administration, and the efficacy of ISDN 2 h and 6 h after oral ingestion. In the first ingestion NTG significantly improved WTI ( p < 0.0001) by 42.7% after OP, by 46.5% after 80 mg ISDN and by 52.1% after 120 mg. After long-term OP therapy NTG prolonged WTI ( p < 0.01) by 15.6%, during once-daily ISDN treatment, an 80 mg dose prolonged WTI by 22.8% and a dose of 120 mg by 36.5%. However, NTG did not improve WTI in q.i.d. therapy. Six hours after the first 80 mg ISDN ingestion WTI improved ( p < 0.0001) by 66.0%, and after 120 mg by 58.4%. Following once-daily therapy ISDN prolonged WTI ( p < 0.0001) by 27.2% after an 80 mg dose and by 36.2% after a dose of 120 mg. No improvement was observed in q.i.d. treatment. Thus, severe tolerance to ISDN abolishes the anti-ischaemic effects of NTG, and appropriate regimens of ISDN have considerable anti-anginal effects during chronic administration.

[Comparative evaluation of the clinical effectiveness and the adverse effects of three different forms of nitrates in high oral doses in patients with stable angina pectoris]. / Porównawcza ocena skutecznosci klinicznej i dzialan niepozadanych trzech róznych azotanów w wysokich dawkach doustnych u chorych ze stabilna dlawica piersiowa.

UNLABELLED: The aim of this study was the comparative evaluation of antianginal efficacy and the adverse effects of 3 nitrates in oral doses: isosorbide dinitrate 80 mg in slow release form (ISDN-80), nitroglycerin 15 mg--slow release (NITRO-15) and pentaerythritol tetranitrate 100 mg in normal tablets (PENTA-100) in patients (pts) with stable angina pectoris. In a randomized, double-blind, cross-over and placebo (P) controlled study 15 men, with mean age 54.8 +/- 8.0 years, with stable angina, received single doses of: ISDN-80, NITRO-15, PENTA-100 or P. Clinical efficacy of the drugs was evaluated by analysis of the walking times: total (TT), to angina (TA), and to ischemia (TI) on treadmill during stress tests performed 2 and 6 hours (h) after drug ingestion; the adverse effects were registered during 6 h follow up. RESULTS: 2 h after ingestion all 3 study drugs improved significantly: TT, TA and TI in comparison to P. After 6 h the same parameters were improved by: ISDN-80 and NITRO-15, but PENTA-100 improved only TT and TA. After 6 h ISDN-80 significantly improved in comparison to NITRO-15: TT by 19.7% (p < 0.01), TA by 21.2% (p < 0.01) ant TI by 25.0% (p < 0.05), and in comparison to PENTA-100: TT by 32.1% (p < 0.001), TA by 33.4% (p < 0.001) and TI by 41.1% (p < 0.01). After 6 h NITRO-15 significantly improved TI in comparison to PENTA-100 by 13.1% (p < 0.05). The headaches, the most frequent adverse effects, occurred after ingestion of ISDN-80 in 6 pts, NITRO-15 in 4 pts, PENTA-100 in 3 pts and P in 1 pt. Among three evaluated nitrates ISDN-80 significantly improved the effort tolerance and the coronary reserve in the strongest way, NITRO-15 was intermediate in the clinical efficacy, but PENTA-100, the drug with the weakest antianginal efficacy, was the reason of the least number of the adverse effects.

[Anti-ischemic effect of angiotensin-converting enzyme inhibitor, but not vitamin C, in patients with coronary artery disease treated with beta-blockers and nitrates. Randomized, cross-over, double-blind comparison]. / Dzialanie przeciwniedokrwienne inhibitora konwertazy, lecz nie witaminy C, u chorych z choroba wiencowa leczonych lekami beta-adrenolitycznymi i azotanami. Badanie metoda krzyzowa z podwójnie zamaskowana próba.

Anti-ischemic effect of angiotensin-converting enzyme inhibitor--chinapril was examined by exercise tolerance test [ETT] in randomised, cross-over double blind comparison in 20 pts with coronary artery disease treated with beta-blockers and nitrates. After 8 weeks of chinapril treatment maximal work capacity and exercise duration were significantly greater in comparison with baseline values, respectively: 7,8 vs 6,7 METs (p < 0,05) and 416 vs 335 s (p < 0,05). Time to ST segment depression was significantly longer after chinapril treatment: 394 vs 298 s (placebo) p = 0,01) vs 277 s (baseline), p = 0,008. The number of patients with exercise ST depression was significantly lower (63% vs 100%). Rate pressure product wasn't changed after chinapril treatment. Vitamin C therapy did not have influence on ischemia signs in exercise tolerance test.

[Prognostic value of exercise tests performed 3 months after coronary artery grafting in evaluation cardiac events. 6 years follow-up]. / Prognostyczna wartosc próby wysilkowej wykonanej w 3 miesiace po operacji wszczepienia pomostów aortalno-wiencowych w ocenie zdarzen sercowych. Obserwacja 6-letnia.

Prognostic value of exercise test in evaluation of cardiac events were examined in 326 pts after coronary artery bypass grafting (CABG). During 6 years follow up 18 (5.5%) cardiac deaths and 23 (7.1%) myocardial infarctions were observed. Chest pains persisted in 116 pts (35.6%) and 37 (11.3%) pts needed hospital treatment. Coronary and bypass angiography were performed in 25 pts (7.7%) followed by PTCA in 8 pts (2.5%) and CABG in 5 (1.5%) pts. Exercise duration and maximal work capacity in exercise tests were significantly lower in pts with cardiac events. Reasons of exercise termination: ST segment depression, heart rate and blood pressure values were not different in pts with and without cardiac events and didn't have prognostic value. Patients with cardiac events had significantly reduced left ventricle function. The value of ejection fraction influenced significantly relative risk of cardiac death (p < 0.05).