[Arrhythmias in thyroid dysfunction]. / Arrhythmien bei Schilddrüsenerkrankungen.

Thyroid dysfunction is associated with characteristic changes in heart rate and arrhythmias. Thyroid hormones act through genomic and non-genomic effects on myocytes and influence contractility, relaxation and action potential duration through a variety of mechanisms. Atrial fibrillation is the most common arrhythmia associated with thyroid dysfunction, it occurs in both euthyroidism and hyperthyroidism in clear association with T4 levels. Mechanistically, in the hyperthyroid state, increased automaticity and triggered activity, together with a shortened refractory period and slowing of the conduction speed, lead to the initiation and maintenance of multiple intraatrial reentry circuits. Influences from the autonomic nervous system and hemodynamics controlled by thyroid hormones act as modulators for arrhythmias, which are promoted by a corresponding substrate (significant impact of comorbidities). Concerning therapy, in addition to treating hyperthyroidism, the initial therapeutic focus is on adequate rate control and anticoagulation in patients with a high risk of thromboembolism. Ablation of atrial fibrillation can be considered later on, although there is an increased likelihood of recurrence compared to patients without hyperthyroidism.Prolongation of the QT interval and increase in QT dispersion are involved in the formation of ventricular arrhythmias. Epidemiological data suggest an association of elevated T4 levels with ventricular arrhythmias and sudden cardiac death. However, this seems to be mainly relevant for patients with underlying cardiac disease (e.g. ICD users).

Impact of the 2022 pulmonary hypertension definition on haemodynamic classification and mortality in patients with aortic stenosis undergoing valve replacement.

Aims: With the 2022 pulmonary hypertension (PH) definition, the mean pulmonary artery pressure (mPAP) threshold for any PH was lowered from ≥25 to >20 mmHg, and the pulmonary vascular resistance (PVR) value to differentiate between isolated post-capillary PH (IpcPH) and combined pre- and post-capillary PH (CpcPH) was reduced from >3 Wood units (WU) to >2 WU. We assessed the impact of this change in the PH definition in aortic stenosis (AS) patients undergoing aortic valve replacement (AVR). Methods and results: Severe AS patients (n = 503) undergoing pre-AVR cardiac heart catheterization were classified according to both the 2015 and 2022 definitions. The post-AVR mortality [median follow-up 1348 (interquartile range 948-1885) days] was assessed. According to the 2015 definition, 219 (44% of the entire population) patients had PH: 63 (29%) CpcPH, 125 (57%) IpcPH, and 31 (14%) pre-capillary PH. According to the 2022 definition, 321 (+47%) patients were diagnosed with PH, and 156 patients (31%) were re-classified: 26 patients from no PH to IpcPH, 38 from no PH to pre-capillary PH, 38 from no PH to unclassified PH, 4 from pre-capillary PH to unclassified PH, and 50 from IpcPH to CpcPH (CpcPH: +79%). With both definitions, only the CpcPH patients displayed increased mortality (hazard ratios ≈ 4). Among the PH-defining haemodynamic components, PVR was the strongest predictor of death. Conclusion: In severe AS, the application of the 2022 PH definition results in a substantially higher number of patients with any PH as well as CpcPH. With either definition, CpcPH patients have a significantly increased post-AVR mortality.

ECG left ventricular hypertrophy in aortic stenosis: Relationship with cardiac structure, invasive hemodynamics, and long-term mortality.

BACKGROUND: In aortic stenosis (AS), left ventricular hypertrophy (LVH) is the response to pressure overload and represents the substrate for a maladaptive cascade, the so-called AS-related cardiac damage. We hypothesized that in AS patients electrocardiogram (ECG) LVH not only predicts echocardiography LVH but also other noninvasive and invasive markers of cardiac damage and prognosis after aortic valve replacement (AVR). METHODS: In 279 patients with severe AS undergoing ECG, echocardiography, and cardiac catheterization before AVR, the Sokolow-Lyon index, the Cornell product, the Romhilt-Estes score, and the Peguero-Lo Presti score were assessed. RESULTS: The mean left ventricular mass index was 109 ± 34 g/m2 , and 131 (47%) patients had echocardiography LVH. The areas under the receiver operator characteristics curve (AUC) for the Sokolow-Lyon index, the Cornell product, the Romhilt-Estes score, and the Peguero-Lo Presti score for the prediction of echocardiography LVH were 0.59, 0.70, 0.63, and 0.65. The Peguero-Lo Presti score had the numerically greatest AUC for the prediction of left ventricular end-diastolic pressure >15 mmHg, mean pulmonary artery wedge pressure >15 mmHg, pulmonary vascular resistance >3 Wood units, mean right atrial pressure >14 mmHg, and stroke volume index <31 mL/m2 . After a median follow-up of 1365 (interquartile range: 931-1851) days after AVR only the Peguero-Lo Presti score was significantly associated with all-cause mortality [hazard ratio: 1.24 (95% confidence interval: 1.01-1.54); per 1 mV increase; p = .045]. CONCLUSIONS: Among severe AS patients, the Peguero-Lo Presti score is associated with abnormalities in cardiac structure including LVH, invasive measures of cardiac damage, and long-term mortality after AVR.

Pulmonary and Systemic Hemodynamics in Patients with Hyperthyroidism.

BACKGROUND: There is an association between hyperthyroidism and pulmonary hypertension. However, the prevalence of pulmonary hypertension in hyperthyroidism and the underlying mechanisms are incompletely defined. METHODS: Consecutive patients with severe hyperthyroidism, mostly due to Graves disease, were included in this single-center study. Echocardiographic assessment of pulmonary hemodynamics was performed at the time of hyperthyroidism diagnosis (baseline) and after normalization of thyroid hormones (follow-up; median 11 months). In a subset of patients, right heart catheterization and noninvasive assessment of central hemodynamics was performed. RESULTS: Among all 99 patients, 31% had pulmonary hypertension at baseline. The estimated systolic pulmonary artery pressure correlated significantly with the estimated left ventricular filling pressure (E/e'). The invasively measured systolic pulmonary artery pressure correlated well with the estimated systolic pulmonary artery pressure. Cardiac output, E/e', left and right ventricular dimensions were significantly reduced from baseline to follow-up, whereas the estimated pulmonary vascular resistance did not differ. Diastolic blood pressure was significantly higher at follow-up, with no change in systolic blood pressure. The central systolic blood pressure, however, exhibited a trend for a reduction at follow-up, while the pulse wave velocity was significantly lower at follow-up. CONCLUSIONS: Approximately one-third of patients with hyperthyroidism have evidence of pulmonary hypertension. Our data suggest that an increased cardiac output and left ventricular filling pressure are the main mechanisms underlying the elevated systolic pulmonary artery pressure in hyperthyroidism, whereas there is no evidence of significant pulmonary vascular disease.

Follow-up of CRT-D patients downgraded to CRT-P at the time of generator exchange.

Background: Some patients with cardiac resynchronisation therapy (CRT) experience super-response (LVEF improvements to ≥50%). At generator exchange (GE), downgrading (DG) from CRT-defibrillator (CRT-D) to CRT-pacemaker (CRT-P) could be an option for these patients on primary prevention ICD indication and no required ICD therapies. Long-term data on arrhythmic events in super-responders is scarce. Methods: CRT-D patients with LVEF improvement to ≥50% at GE were identified in four large centres for retrospective analysis. Mortality, significant ventricular tachyarrhythmia and appropriate ICD-therapy were determined, and patient analysis was split into two groups (downgraded to CRT-P or not). Results: Sixty-six patients (53% male, 26% coronary artery disease) on primary prevention were followed for a median of 129 months [IQR: 101-155] after implantation. 27 (41%) patients were downgraded to CRT-P at GE after a median of 68 [IQR: 58-98] months (LVEF 54% ± 4%). The other 39 (59%) continued with CRT-D therapy (LVEF 52% ± 6%). No cardiac death or significant arrhythmia occurred in the CRT-P group (median follow-up (FU) 38 months [IQR: 29-53]). Three appropriate ICD-therapies occurred in the CRT-D group [median FU 70 months (IQR: 39-97)]. Annualized event-rates after DG/GE were 1.5%/year and 1.0%/year in the CRT-D group and the whole cohort, respectively. Conclusions: No significant tachyarrhythmia were detected in the patients downgraded to CRT-P during follow-up. However, three events were observed in the CRT-D group. Whilst downgrading CRT-D patients is an option, a small residual risk for arrhythmic events remains and decisions regarding downgrade should be made on a case-by-case basis.

Systemic blood pressure in severe aortic stenosis: Haemodynamic correlates and long-term prognostic impact.

AIMS: Blood pressure (BP) targets in patients with aortic stenosis (AS) are controversial. This study sought to describe the haemodynamic profile and the clinical outcome of severe AS patients with low versus high central meaarterial pressure (MAP). METHODS AND RESULTS: Patients with severe AS (n = 477) underwent right and left heart catheterization prior to aortic valve replacement (AVR). The population was divided into MAP quartiles. The mean systolic BP, diastolic BP, and MAP in the entire population were 149 ± 25, 68 ± 11, and 98 ± 14 mmHg. Patients in the lowest MAP quartile had the lowest left ventricular ejection fraction (LVEF), systemic vascular resistance, and valvulo-arterial impedance, whereas there were no significant differences in mean right atrial pressure, mean pulmonary artery wedge pressure, pulmonary vascular resistance, and stroke volume index across MAP quartiles. However, left ventricular stroke work index (LVSWI) was lowest in patients in the lowest and highest in those in the highest MAP quartile. After a median (interquartile range) post-AVR follow-up of 3.7 (2.6-5.2) years, mortality was highest in patients in the lowest MAP quartile [hazard ratio 3.08 (95% confidence interval 1.21-7.83); P = 0.02 for lowest versus highest quartile]. In the multivariate analysis, lower MAP [hazard ratio 0.78 (95% confidence interval 0.62-0.99) per 10 mmHg increase; P = 0.04], higher mean right atrial pressure and lower LVEF were independent predictors of death. CONCLUSIONS: In severe AS patients, lower MAP reflects lower systemic vascular resistance and valvulo-arterial impedance, which may help to preserve stroke volume and filling pressures despite reduced left ventricular performance, and lower MAP is a predictor of higher long-term post-AVR mortality.

[Therapy of Heart Failure with Reduced Ejection Fraction: What's New in the 2021 Guidelines?] / Therapie der Herzinsuffizienz mit reduzierter Auswurffraktion: Was ist neu in den Leitlinien 2021?

Therapy of Heart Failure with Reduced Ejection Fraction: What's New in the 2021 Guidelines? Abstract. The spectrum of treatment options for patients with heart failure with reduced ejection fraction (HFrEF) has substantially expanded over the last years. The 2021 guidelines of the European Society of Cardiology propose a new treatment algorithm for patients with HFrEF and define the role of the currently available drugs, interventions and devices in this context. The new standard is a basic therapy consisting of four drugs with different mechanisms of action for all patients with HFrEF: an angiotensin-converting enzyme inhibitor, a betablocker, a mineralocorticoid antagonist, and a sodium glucose co-transporter-2 inhibitor. Additional drugs and/or interventions/devices are indicated depending on the response to the four-drug basic therapy (which has to be up-titrated to the maximally tolerated doses) and the clinical phenotype. In the present article, we discuss the available drugs and devices, their role in the proposed HFrEF treatment algorithm and clinically relevant practical aspects.

Electrocardiographic alterations by pneumothorax: a case-control study with review of the literature.

BACKGROUND: Numerous ECG alterations due to pneumothorax have been reported. The objective of the study was to establish the presence of ECG changes associated with pneumothorax in the literature, and in a cohort of patients with proven pneumothorax compared with age- and sex-matched healthy controls. METHODS: A systematic review for ECG alterations associated with pneumothorax was performed. We then reviewed our hospital database for patients with pneumothorax and identified all patients with an ECG available at this time. The retrieved ECG alterations in the systematic review were identified in our pneumothorax patients and compared with a healthy sex- and age-matched control group. Accordingly, we calculated sensitivity and specificity for all alterations. RESULTS: Seventeen ECG alterations were found and defined from the systematic review. Our pneumothorax cohort consisted of 82 pneumothorax patients and 82 control patients. Specificity was mostly more than 90%, but sensitivities were low. Phasic R voltage (pneumothorax group 25.6% vs control group 1.2%), T-wave inversion (31.7% vs 2.4%), prolonged QTc (11.0% vs 2.4%), right axis deviation (14.6% vs 3.6%) and QRS voltage ratio in aVF/I >2 (41.5% vs 22.0%) were significantly more frequent in pneumothorax patients compared with controls. CONCLUSION: The sensitivity of published ECG signs in predicting pneumothorax in our cohort was low, which means that ECG findings are an unsuitable tool for pneumothorax screening. However, presence of these ECG signs might raise a suspicion of pneumothorax in patients presenting with dyspnoea, or unclear chest discomfort.

Pulmonary Hypertension in Patients With Heart Failure With Mid-Range Ejection Fraction.

Pulmonary hypertension (PH) is common in patients with heart failure (HF). The role of PH in patients with HF with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction (LVEF) has been extensively characterized during the last years. In contrast, the pathophysiology of HF with mid-range LVEF (HFmrEF), and in particular the role of PH in this context, are largely unknown. There is a paucity of data in this field, and the prevalence of PH, the underlying mechanisms, and the optimal therapy are not well-defined. Although often studied together there is increasing evidence that despite similarities with both HFrEF and HFpEF, HFmrEF also differs from both entities. The present review provides a summary of the current concepts of the mechanisms and clinical impact of PH in patients with HFmrEF, a proposal for the non-invasive and invasive diagnostic approach required to define the pathophysiology of PH and its management, and a discussion of future directions based on insights from mechanistic studies and randomized trials. We also provide an outlook regarding gaps in evidence, future clinical challenges, and research opportunities.

Corrected QT Interval in Severe Aortic Stenosis: Clinical and Hemodynamic Correlates and Prognostic Impact.

BACKGROUND: The role of the electrocardiogram for risk stratification in patients with severe aortic stenosis is not established. We assessed the hemodynamic correlates and the prognostic value of the corrected QT interval (QTc) in patients with severe aortic stenosis undergoing aortic valve replacement. METHODS: The QT interval was measured in a 12-lead electrocardiogram in 485 patients (age 74 ± 10 years, 57% male) with severe aortic stenosis (indexed aortic valve area 0.41 ± 0.13 cm2/m2, left ventricular ejection fraction 58 ± 12%) the day prior to cardiac catheterization. Prolonged QTc was defined as QTc >450 ms in men and QTc >470 ms in women. The outcome parameter was all-cause mortality. RESULTS: Patients with prolonged QTc (n = 100; 77 men, 23 women) had similar indexed aortic valve area but larger left ventricular and left atrial size, lower left ventricular ejection fraction, more severe mitral regurgitation, lower cardiac index, and higher mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and pulmonary vascular resistance, as compared with patients with normal QTc (n = 385). After a median follow-up of 3.7 years (interquartile range, 2.6-5.2) after surgical (n = 349) or transcatheter (n = 136) aortic valve replacement, patients with prolonged QTc had higher mortality than those with normal QTc (hazard ratio 2.81 [95% confidence interval, 1.51-5.20]; P < .001). Prolonged QTc was an independent predictor of death along with more severe mitral regurgitation and higher pulmonary vascular resistance. CONCLUSIONS: In patients with severe aortic stenosis, prolonged QTc is a marker of an advanced disease stage associated with an adverse hemodynamic profile and increased long-term mortality after aortic valve replacement.

Use of the wearable cardioverter-defibrillator - the Swiss experience.

INTRODUCTION: Sudden cardiac death caused by malignant arrhythmia can be prevented by the use of defibrillators. Although the wearable cardioverter defibrillator (WCD) can prevent such an event, its role in clinical practice is ill defined. We investigated the use of the WCD in Switzerland with emphasis on prescription rate, therapy adherence and treatment rate. MATERIALS AND METHODS: The Swiss WCD Registry is a retrospective observational registry including patients using a WCD. Patients were included from the first WCD use in Switzerland until February 2018. Baseline characteristics and data on WCD usage were examined for the total study population, and separately for each hospital. RESULTS: From 1 December 2011 to 18 February 2018, a total of 456 patients (67.1% of all WCDs prescribed in Switzerland and 81.1% of all prescribed in the participating hospitals) were included in the registry. Up to 2017 there was a yearly increase in the number of prescribed WCDs to a maximum of 271 prescriptions per year. The mean age of patients was 57 years (± 14), 81 (17.8%) were female and mean left ventricular ejection fraction (EF) was 32% (± 13). The most common indications for WCD use were new-onset ischaemic cardiomyopathy (ICM) with EF ≤35% (206 patients, 45.2%), new-onset nonischaemic cardiomyopathy (NICM) with EF ≤35% (115 patients, 25.2%), unknown arrhythmic risk (83 patients, 18.2%), bridging to implantable cardioverter-defibrillator implantation or heart transplant (37 patients, 8.1%) and congenital/inherited heart disease (15 patients, 3.3%). Median wear duration was 58 days (interquartile range [IQR] 31–94) with a median average daily wear time of 22.6 hours (IQR 20–23.2). Seventeen appropriate therapies from the WCD were delivered in the whole population (treatment rate: 3.7%) to a total of 12 patients (2.6% of all patients). The most common underlying heart disease in patients with a treatment was ICM (13/17, 76.5%). There were no inappropriate treatments. CONCLUSION: The use of WCDs has increased in Switzerland over the years for a variety of indications. There is high therapy adherence to the WCD, and a treatment rate comparable to previously published registry data.  .

Hemodynamic profile of patients with severe aortic valve stenosis and atrial fibrillation versus sinus rhythm.

BACKGROUND: In patients with severe aortic stenosis (AS), atrial fibrillation (AF) is associated with increased long-term mortality after aortic valve replacement (AVR), which may be due to unfavorable hemodynamics in AF. We aimed to analyze the hemodynamic profile of patients with severe AS and AF versus sinus rhythm (SR). METHODS: We performed cardiac catheterization in 486 patients (age 74 ±â€¯10 years, 58% males) with severe AS [indexed aortic valve area 0.41 ±â€¯0.13 cm2, left ventricular ejection fraction 58 ±â€¯12%]: 50 patients had AF, and 436 patients had SR. All patients underwent surgical (n = 350) or transcatheter (n = 136) AVR. RESULTS: Despite similar indexed aortic valve area (0.41 ±â€¯0.11 vs. 0.41 ±â€¯0.12 cm2/m2; p = 0.45) patients with AF had lower left ventricular ejection fraction, larger left atrial size, lower tricuspid annular plane systolic excursion, higher mean pulmonary artery pressure (34 ±â€¯13 vs. 24 ±â€¯9 mmHg), mean pulmonary artery wedge pressure (mPAWP; 22 ±â€¯8 vs. 15 ±â€¯7 mmHg), and pulmonary vascular resistance (2.8 ±â€¯1.9 vs. 2.0 ±â€¯1.3 Wood units) and lower stroke volume index (26 ±â€¯9 vs. 37 ±â€¯10 ml/m2) than patients with SR (p < 0.05 for all). Patients with AF and SR had a different mPAWP-left ventricular end-diastolic pressure (LVEDP) relationship with higher mPAWP in AF and higher LVEDP in SR. After a median follow-up of 49 (interquartile range, 35-64) months post-AVR patients with AF (p = 0.05) and patients with a larger difference between mPAWP and LVEDP (p = 0.005) had higher mortality. CONCLUSIONS: Patients with severe AS and concomitant AF have a distinct and significantly worse hemodynamic profile compared to patients with SR associated with worse clinical outcome.

Relationship between B-type natriuretic peptide and invasive haemodynamics in patients with severe aortic valve stenosis.

AIMS: In patients with aortic stenosis (AS), B-type natriuretic peptide (BNP) is a prognostic marker. However, there is little information on the association between BNP and invasive haemodynamics in AS. The aim of the present study was to assess the hitherto not well-defined relationship between BNP and invasive haemodynamics in patients with severe AS undergoing aortic valve replacement (AVR) with a view to understand the link between high BNP and poor prognosis in these patients. In particular, we were interested in the association between BNP and combined pre-capillary and post-capillary pulmonary hypertension (CpcPH). METHODS AND RESULTS: BNP was measured in 252 patients (age 74 ± 10 years, 58% male patients) with severe AS [indexed aortic valve area 0.4 ± 0.1 cm2 /m2 and left ventricular ejection fraction (LVEF) 57 ± 12%] the day before cardiac catheterization. Patients were followed for a median (interquartile range) period of 3.1 (2.3-4.3) years after surgical (n = 157) or transcatheter (n = 95) AVR. The prevalence of CpcPH (mean pulmonary artery pressure ≥ 25 mmHg, mean pulmonary artery wedge pressure > 15 mmHg, and pulmonary vascular resistance > 3 Wood units) was 13%. The median BNP plasma concentration was 188 (78-452) ng/L. The indexed aortic valve area was similar across BNP quartiles (P = 0.21). Independent predictors of higher BNP (ln transformed) included lower haemoglobin (beta = -0.18; P < 0.001), lower LVEF (beta = -0.20; P < 0.001), more severe mitral regurgitation (beta = 0.20; P < 0.001), higher mean pulmonary artery wedge pressure (beta = -0.37; P < 0.001), and higher pulmonary vascular resistance (beta = 0.21; P < 0.001). In a multivariate model with CpcPH rather than its haemodynamic components, CpcPH was independently associated with higher BNP (0.21; P < 0.001). Higher ln BNP was associated with higher mortality [hazard ratio 1.90 (95% confidence interval 1.33-2.71); P < 0.001] in the univariate analysis. Patients in the third and fourth BNP quartiles had a more than six-fold risk of death compared with patients in the first and second quartiles [hazard ratio 6.29 (95% confidence interval 1.86-21.27); P = 0.003]. In the multivariate analysis, lower LVEF [hazard ratio 0.96 (95% confidence interval 0.94-0.99) per 1% increase; P = 0.01] and CpcPH [hazard ratio 4.58 (95% confidence interval 1.89-11.09); P = 0.001] but not BNP were independently associated with mortality. The areas under the receiver operator characteristics curve for BNP for the prediction of CpcPH and mortality were 0.88 and 0.74, respectively. CONCLUSIONS: In patients with severe AS, higher BNP is a marker of the presence of CpcPH and its contributors. The association between BNP and such an adverse haemodynamic profile at least in part explains the ability of BNP to predict long-term post-AVR mortality.

The Medtronic Sprint Fidelis® lead history revisited-Extended follow-up of passive leads.

BACKGROUND: Due to high failure rates, Medtronic withdrew the Sprint Fidelis lead (SFL) from the market. Passive fixation lead models exhibited better survival than active models, but most studies have limited follow-up. Aim of this study was to give insights into passive lead survival with a follow-up of 10 years. METHODS: In two large Swiss centers, patients with passive SFLs were identified and data from routine implantable cardioverter defibrillator (ICD) follow-ups were collected. Patients were censored at time of death, last device interrogation (if lost to follow-up), time of lead revision (in non-SFL-related problems), or at database closure (31th December 2017). We defined lead failure as any of the following: lead fracture with inappropriate discharge; sudden increase in low-voltage impedance to >1500 or high-voltage impedance to >100 Ω; >300 nonphysiological short VV-intervals. RESULTS: We identified 145 patients. Age at implant was 60 ± 12 years with a median follow-up of 10.2 (interquartile range [IQR]: 5.0-11.2) years. Thirty-five percent of patients died after 5.4 ± 2.7 years. A total of 19 leads (13%) failed after 6.7 ± 3.2 years (range: 1.2-12.0). Overt malfunction with shocks existed in four patients (3%). Cumulative lead survival was 93.1% at 6, 88.2% at 8, 83.8% at 10, and 77.6% at 11 years, respectively, with 35% of implanted leads under monitoring at 10 years. Lead survival fits best a Weibull distribution with accelerating failure rates (k = 1.95, 95% CI 1.32-2.87, P < 0.001). CONCLUSIONS: During very long-term follow-up, failure rate of the passive SFL shows an increase resulting in an impaired lead survival of 84% at 10 years.

[Follow-up of Patients with Cardiac Pacemakers]. / CME: Nachkontrollen bei Schrittmacher-Patienten.

Follow-up of Patients with Cardiac Pacemakers Abstract. General practitioners play a central role for patients with cardiac pacemakers (PM) because they are mostly the first medical professionals confronted with PM problems. Acute dyspnea, dizzy spells/fainting or infection of the device pocket are red flags in the first weeks after PM implantation and warrant urgent workup. Symptoms late after PM implantation are less overtly associated with the PM. Routine follow-up examinations include an inspection of the PM pocket and an ECG, which has to be interpreted with the knowledge of the PM function and PM programming. Frequently, a PM interrogation will be necessary to achieve a correct diagnosis and initiate the appropriate management.

Haemodynamic mechanisms and long-term prognostic impact of pulmonary hypertension in patients with severe aortic stenosis undergoing valve replacement.

AIMS: We aimed to investigate the prevalence, detailed invasive haemodynamics, and prognostic impact of pulmonary hypertension (PH) in severe aortic stenosis (AS). METHODS AND RESULTS: We studied 503 patients (mean age 74 ± 10 years) with severe AS (indexed aortic valve area 0.4 ± 0.1 cm2 /m2 , left ventricular ejection fraction 57 ± 12%) undergoing left and right heart catheterization prior to aortic valve replacement. Median follow-up was 3.7 (interquartile range 2.6-5.4) years. Baseline PH (mean pulmonary artery pressure ≥ 25 mmHg) was found in 239 (48%) patients: 31 patients had pre-capillary PH [mean pulmonary artery wedge pressure (mPAWP) ≤ 15 mmHg], 144 had isolated post-capillary PH [IpcPH; mPAWP > 15 mmHg, pulmonary vascular resistance (PVR) ≤ 3 Wood units (WU)], and 64 had combined pre- and post-capillary PH (CpcPH; mPAWP > 15 mmHg, PVR > 3 WU). Patients with CpcPH had higher mortality than those with IpcPH, pre-capillary PH, and without PH. In the multivariate analysis, CpcPH remained an independent predictor of death (hazard ratio 4.39, 95% confidence interval 2.40-8.03; P < 0.001). Patients with CpcPH had higher mPAWP (26 ± 7 vs. 22 ± 5 mmHg) and lower pulmonary arterial capacitance (1.5 ± 0.6 vs. 2.9 ± 1.2 mL/mmHg) than IpcPH patients but similar left ventricular end-diastolic pressure (LVEDP; 25 ± 7 vs. 25 ± 7 mmHg). A smaller LVEDP-mPAWP difference was related to larger left atrial size, atrial fibrillation, and more severe mitral regurgitation. CONCLUSIONS: In patients with severe AS, PH is common but underlying mechanisms differ. Patients with CpcPH have higher mPAWP, lower pulmonary arterial capacitance, and worse survival than all other groups. Left atrial dysfunction and mitral regurgitation seem to be drivers of high mPAWP in CpcPH.

[Heart failure with preserved ejection fraction (HFpEF)]. / Herzinsuffizienz mit erhaltener linksventrikulärer Auswurffraktion (HFpEF).

Heart failure with preserved ejection fraction (HFpEF) Abstract. Heart failure with preserved left ventricular ejection fraction (HFpEF) is a very common form of heart failure typically seen in older patients and associated with poor prognosis. Patients with HFpEF are characterized by a s small left ventricle with concentric remodeling and abnormal compliance, which under the impact of additional cardiovascular mechanisms and non-cardiac comorbidities, leads to the cardinal symptoms of dyspnea and exercise intolerance. The diagnosis of HFpEF is still under debate, and the therapeutic options are limited despite intensive research efforts. In the present review article, we provide an overview of the current understanding of the pathiohysiology of HFpEF, the current diagnostic approach, and a summary of the available evidence on treatment.

Reduction of falls and fractures after permanent pacemaker implantation in elderly patients with sinus node dysfunction.

AIMS: Elderly patients with sinus node dysfunction (SND) are at increased risk of falls with possible injuries. However, the incidence of these adverse events and its reduction after permanent pacemaker (PPM) implantation are not known. METHODS AND RESULTS: Eighty-seven patients (mean [SD] age 75.4 [8.3] years, 51% women) with SND and an indication for cardiac pacing were included and were examined by a standardized interview targeting fall history. The incidence and total number of falls, falls with injury, falls requiring treatment, and falls resulting in a fracture were assessed for the time period of 12 months before (retrospectively) and after PPM implantation (prospectively). Furthermore, symptoms such as syncope, dizziness, and dyspnea were evaluated before and after PPM implantation. The implantation of a PPM was associated with a reduced proportion of patients experiencing at least one fall by 71% (from 53 to 15%, P < 0.001) and a reduction of the absolute number of falls by 90% (from 127 to 13, P < 0.001) during the 12 months before vs. after PPM implant. Falls with injury (28 vs. 10%, P = 0.005), falls requiring medical attention (31 vs. 8%, P < 0.001), and falls leading to fracture (8 vs. 0%, P = 0.013) were similarly reduced. Notably, fewer patients had syncope (4 vs. 45%, P < 0.001) and dizziness after PPM implantation (12 vs. 45%, P < 0.001). CONCLUSION: Falls, fall-related injuries, and fall-related fractures are frequent in SND patients. Permanent pacemaker implantation is associated with a significantly reduced risk of these adverse events, although no causal relationship could be established due to the study design.

Mediation of coffee-induced improvements in human vascular function by chlorogenic acids and its metabolites: Two randomized, controlled, crossover intervention trials.

BACKGROUND & AIMS: Polyphenol intake has been linked to improvements in human vascular function, although data on hydroxycinnamates, such as chlorogenic acid (CGA) have not yet been studied. We aimed to investigate the impact of coffee intake rich in chlorogenic acid on human vascular function and whether CGAs are involved in potential effects. METHODS: Two acute randomized, controlled, cross-over human intervention trials were conducted. The impact of coffee intake, matched for caffeine but differing in CGA content (89, and 310 mg) on flow-mediated dilatation (FMD) was assessed in 15 healthy male subjects. In a second intervention trial conducted with 24 healthy male subjects, the impact of pure 5-caffeoylquinic acid (5-CQA), the main CGA in coffee (5-CQA; 450 mg and 900 mg) on FMD was also investigated. RESULTS: We observed a bi-phasic FMD response after low and high polyphenol, (89 mg and 310 mg CGA) intake, with increases at 1 (1.10 ± 0.43% and 1.34 ± 0.62%, respectively) and 5 (0.79% ± 0.32 and 1.52% ± 0.40, respectively) hours post coffee consumption. FMD responses to coffee intake was closely paralleled by the appearance of CGA metabolites in plasma, notably 3-, 4- and 5-feruloylquinic acid and ferulic-4'-O-sulfate at 1 h and isoferulic-3'-O-glucuronide and ferulic-4'-O-sulfate at 5 h. Intervention with purified 5-CQA (450 mg) also led to an improvement in FMD response relative to control (0.75 ± 1.31% at 1 h post intervention, p = 0.06) and concomitant appearance of plasma metabolites. CONCLUSIONS: Coffee intake acutely improves human vascular function, an effect, in part, mediated by 5-CQA and its physiological metabolites. STUDY REGISTRATION: The National Institutes of Health (NIH) on ClinicalTrials.govNCT01813981 and NCT01772784.