Ultra-long-term efficacy and safety of catheter-based renal denervation in resistant hypertension: 10-year follow-up outcomes.

BACKGROUND: Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce. AIMS: This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension. METHODS: This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years. RESULTS: Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7 years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23 mmHg and 153 ± 16 mmHg, respectively. After 10 years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17 mmHg (P < 0.001) and 14 ± 23 mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60 mL/min/1.73m2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up. CONCLUSION: Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10 years in patients with resistant hypertension.

Outcomes of left bundle branch area pacing compared to His bundle pacing as a primary pacing strategy: Systematic review and meta-analysis.

BACKGROUND: Novel pacing technologies, such as His bundle pacing (HBP) and left bundle branch area pacing (LBBaP), have emerged to maintain physiological ventricular activation. We investigated the outcomes of LBBP with HBP for patients requiring a de novo permanent pacing. METHODS AND RESULTS: Systematic review of randomized clinical trials and observational studies comparing LBBaP with HBP until March 01, 2023 was performed. Random and fixed effects meta-analyses of the effect of pacing technology on outcomes were performed. Study outcomes included pacing metrics, QRS duration, lead revision, procedure parameters, all-cause mortality and heart failure hospitalization (HFH). Overall, 10 studies with 1596 patients were included. Implant success rate was higher in LBBaP compared with HBP (RR 1.24, 95% CI: 1.08 to 1.42, p = .002). LBBaP was associated with lower capture threshold at implantation (mean difference (MD) -0.62 V, 95% CI: -0.74 to -0.51 V, p < .0001) and at follow-up (MD -0.74 V, 95% CI: -0.96 to -0.53, p < .0001), shorter procedure duration (MD -14.66 min, 95% CI: -23.54 to -5.78, p = .001) and shorter fluoroscopy time (MD -4.2 min, 95% CI: -8.4 to -0.0, p = .05). Compared with HBP, LBBaP was associated with a decreased risk of all-cause mortality (RR: 0.50, 95% CI: 0.33 to 0.77, p = .002) and HFH (RR: 0.57, 95% CI: 0.33 to 1.00, p = .05). No statistical differences were found in lead revisions and QRS duration before and after pacing. CONCLUSION: This meta-analysis found that LBBaP was superior to HBP regarding pacing metrics and implant success rate as an initial pacing strategy, although absence of head-to-head randomized comparison warrants caution in interpretation of the results.

A randomized, placebo-controlled, trial to assess the photosensitizing, phototoxic and carcinogenic potential of hydrochlorothiazide in healthy volunteers.

BACKGROUND AND AIMS: Pharmacovigilance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blind trial in vivo and also in vitro . METHODS: The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis. RESULTS: Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm 2 vs. placebo 0.0 J/cm 2 ; P  = 0.99; UVB change HCT 0.0 J/cm 2 vs. placebo -0.2 J/cm 2 ; P  = 0.06). Pyrimidine dimers were not detected in either group. In vitro , combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins. CONCLUSION: HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro , HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312).

Impedance-based remote monitoring in patients with heart failure and concomitant chronic kidney disease.

AIMS: Remote monitoring (RM) of thoracic impedance represents an early marker of pulmonary congestion in heart failure (HF). Chronic kidney disease (CKD) may promote fluid overload in HF patients. We investigated whether concomitant CKD affected the efficacy of impedance-based RM in the OptiLink HF trial. METHODS AND RESULTS: Among HF patients included in the OptiLink HF trial, time to the first cardiovascular hospitalization and all-cause death according to the presence of concomitant CKD was analysed. CKD was defined as GFR < 60 mL/min/1.73 m2 at enrolment. Of the 1002 patients included in OptiLink HF, 326 patients (33%) had HF with concomitant CKD. The presence of CKD increased transmission of telemedical alerts (median of 2 (1-5) vs. 1 (0-3); P = 0.012). Appropriate contacting after alert transmission was equally low in patients with and without CKD (57% vs. 59%, P = 0.593). The risk of the primary endpoint was higher in patients with CKD compared with patients without CKD (hazard ratio (HR), 1.62 [95% confidence interval (CI), 1.16-2.28]; P = 0.005). Impedance-based RM independently reduced primary events in HF patients with preserved renal function, but not in those with CKD (HR 0.68 [95% CI, 0.52-0.89]; P = 0.006). CONCLUSIONS: The presence of CKD in HF patients led to a higher number of telemedical alert transmissions and increased the risk of the primary endpoint. Inappropriate handling of alert transmission was commonly observed in patients with chronic HF and CKD. Guidance of HF management by impedance-based RM significantly decreased primary event rates in patients without CKD, but not in patients with CKD.

Mapping of an atrial tachycardia after Epicor™ high-intensity focused ultrasound ablation: A case report.

BACKGROUND: Surgical techniques, such as the application of high-intensity focused ultrasound (HIFU), can be used for pulmonary vein isolation (PVI). CASE SUMMARY: We report a case of a 73-year old patient, in whom HIFU failed to achieve PVI but promoted the occurrence of a scar-related atrial tachycardia (AT). Voltage mapping of the left atrium revealed multiple gaps along the ablation line. Coherent mapping with visualization of velocity vectors allowed the correct interpretation and the targeted ablation of the AT. DISCUSSION: Cardiac surgery can promote scar-related AT. The coherent mapping function could simplify the mapping of scar-related AT in the future.

Cardiovascular Outcomes According to Polypharmacy and Drug Adherence in Patients with Atrial Fibrillation on Long-Term Anticoagulation (from the RE-LY Trial).

Prevalence of atrial fibrillation (AF) increases with age, along with comorbidities and, thus, polypharmacy. Non-adherence is associated with polypharmacy. This study aimed to identify patients at risk for cardiovascular events according to their pharmacological treatment intensity and adherence. Patients (n = 18,113) with a mean age of 71.5 ± 8.7 years, at high cardiovascular risk were followed between December 2005 until December 2007 for a median time of 2 years. The association between polypharmacy and adherence and their impact on cardiovascular and bleeding events were explored. Adherence was defined as a study drug intake of ≥80%. Patients with more co-medications had a higher body mass index, higher prevalence of hypertension, coronary heart disease, heart failure, and diabetes mellitus (all p < 0.0001) compared to ≤4 or 5-8 co-medications, but no differences in history of stroke (p = 0.68) or transient ischemic attack (p = 0.065). Across all treatments, the adjusted hazard ratios (HRs) increased in patients with more co-medications (≥9 vs ≤4) for all-cause death (HR 1.30; 1.06-1.59), major bleeding (HR 1.65; 1.33-2.05), and all bleeding events (HR 1.44; 1.31-1.59). Yearly event rates were higher in non-adherent than adherent patients for stroke and systemic embolism (SSE) (3.14 vs 1.00), all-cause death (7.76 vs 2.66), major bleeding (6.21 vs 2.65), and all bleeding (28.71 vs 19.05; all p < 0.0001). After an event the patients were more likely to become non-adherent (adherence after SSE 30.3%, after major bleeding 33.4%, after all bleeding 66.7%; all p < 0.0001). The treatment effects were consistent to the overall group in the different polypharmacy groups. In conclusion, polypharmacy and non-adherence are risk indicators for increased adverse cardiovascular and bleeding events. Dabigatran is safe to use across the full spectrum of AF patients, independent of the number of co-medications and adherence. Patients with co-medications and comorbidities require special attention and encouragement to adhere to oral anticoagulation.

Ventricular arrhythmias and myocardial inflammation: Long-term follow-up of patients with suspected myocarditis.

BACKGROUND: Inflammatory heart disease is known to be associated with ventricular arrhythmias (VA) and impaired ventricular function at presentation or during follow-up. We aimed to investigate the need for implanted cardioverter defibrillator (ICD) due to ventricular dysfunction and occurrence of VA during long-term follow-up in patients admitted with suspected myocarditis. METHODS: Between 2000 and 2016, 191 patients (age 43 ±â€¯13 years, 71% male, mean left ventricular ejection fraction (LVEF) 33 ±â€¯15%) with clinically suspected myocarditis, who underwent endomyocardial biopsies (EMB), were prospectively enrolled and followed up in 6-months-intervals (median follow-up was 83 (49-156) months). The primary endpoint was deterioration of cardiac function (LVEF ≤ 35%) or occurrence of VA leading to ICD implantation. RESULTS: According to EMB results, patients were stratified in three diagnostic groups: acute myocarditis (5%), chronic myocarditis (50%) and dilated cardiomyopathy (DCM) (45%). An ICD implantation was performed in 58 patients (30%, n = 38 for primary prevention). Besides LVEF at baseline, chronic myocardial inflammation was the only independent predictor of ICD implantation for primary prevention (hazard ratio 2.48 (95% confidence interval 1.02-5.5); p = 0.045). VA requiring ICD therapy occurred in 29 of 58 patients (50%) after a median of 14 (2-37) months without a significant difference between presence and absence of myocardial inflammation. CONCLUSIONS: Nearly one third of patients with suspected myocarditis require an ICD due to impaired LVEF or occurrence of VA. Half of these patients experienced VA with adequate ICD therapy.

Effects of catheter-based renal denervation on cardiac sympathetic activity and innervation in patients with resistant hypertension.

OBJECTIVES: To investigate, whether renal denervation (RDN) has a direct effect on cardiac sympathetic activity and innervation density. BACKGROUND: RDN demonstrated its efficacy not only in reducing blood pressure (BP) in certain patients, but also in decreasing cardiac hypertrophy and arrhythmias. These pleiotropic effects occur partly independent from the observed BP reduction. METHODS: Eleven patients with resistant hypertension (mean office systolic BP 180 ± 18 mmHg, mean antihypertensive medications 6.0 ± 1.5) underwent I-123-mIBG scintigraphy to exclude pheochromocytoma. We measured cardiac sympathetic innervation and activity before and 9 months after RDN. Cardiac sympathetic innervation was assessed by heart to mediastinum ratio (H/M) and sympathetic activity by wash out ratio (WOR). Effects on office BP, 24 h ambulatory BP monitoring, were documented. RESULTS: Office systolic BP and mean ambulatory systolic BP were significantly reduced from 180 to 141 mmHg (p = 0.006) and from 149 to 129 mmHg (p = 0.014), respectively. Cardiac innervation remained unchanged before and after RDN (H/M 2.5 ± 0.5 versus 2.6 ± 0.4, p = 0.285). Cardiac sympathetic activity was significantly reduced by 67 % (WOR decreased from 24.1 ± 12.7 to 7.9 ± 25.3 %, p = 0.047). Both, responders and non-responders experienced a reduction of cardiac sympathetic activity. CONCLUSION: RDN significantly reduced cardiac sympathetic activity thereby demonstrating a direct effect on the heart. These changes occurred independently from BP effects and provide a pathophysiological basis for studies, investigating the potential effect of RDN on arrhythmias and heart failure.

Angiopoietin-2 and outcome in patients with acute decompensated heart failure.

PURPOSE: Angiopoietin-2 (Ang-2) impairs endothelial integrity. The association of Ang-2 in the presence of oedema and outcome of patients with acute decompensated heart failure (ADHF) has not been investigated. METHODS AND RESULTS: Angiopoietin-2 was measured in 132 ADHF patients, which were included in a monocentric, prospective trial (Clinicaltrials.gov: NCT01429857). Primary endpoint was all-cause death at 6-months. 20 healthy persons served as control group (HC). In ADHF patients, mean Ang-2 concentration at admission was significantly increased compared to HC (2,111 ± 117 vs. 971 ± 46 pg/ml, p = 0.0002). Ang-2 was increased in patients with compared to those without peripheral oedema (2,294 ± 140 vs. 1,540 ± 170 pg/ml; p = 0.009) and in patients with NYHA class III or IV symptoms compared to those with NYHA class II symptoms (2,256 ± 132 vs. 1,341 ± 380 pg/ml, p = 0.023). During the 6-month follow-up, 10 patients died. In survivors, Ang-2 significantly decreased at discharge compared to admission (2,046 ± 118 vs. 1,431 ± 93 pg/ml; p < 0.0001). Non-survivors showed no difference between Ang-2 concentration at admission and discharge (3,296 ± 594 vs. 2,909 ± 536 pg/ml). Ang-2 concentrations at discharge above 2,500 pg/ml were associated with an increased risk of death compared to Ang-2 concentrations below this threshold (Hazard ratio 8.8; 95 % confidence interval; 2.48-31.16, p < 0.001). CONCLUSION: In ADHF patients, Ang-2 is significantly increased compared to healthy controls, shows a relationship in the presence of oedema and is a predictor of poor outcome.

Diagnostic and prognostic validity of different biomarkers in patients with suspected myocarditis.

BACKGROUND: Myocarditis might be associated with increased markers of myocardial injury. However, data on novel biomarkers, such as high-sensitive Troponin T (hs-TnT) or Copeptin, are lacking. This study aimed to determine the diagnostic and prognostic utility of biomarkers in patients with suspected myocarditis. METHODS: Seventy patients with clinically suspected myocarditis (age 43.4 ± 14 years, 76 % male, ejection fraction 36.9 ± 17.8) underwent endomyocardial biopsy (EMB) and were followed for 7.5 (2-21) months. At the time of EMB, blood samples to evaluate concentrations of hs-TnT, Copeptin, NT-proBNP and mid-regional pro-adrenomedullin (MR-proADM) were collected. RESULTS: According to EMB, 6 patients were diagnosed with acute myocarditis (AM) and 36 patients with chronic myocarditis (CM). In 28 patients, EMB revealed no myocardial inflammation (NM). Acute myocarditis was associated with the highest concentrations of hs-TnT compared to other groups (AM 262.9 pg/ml (61.4-884.2); CM 20.4 pg/ml (15.6-20.4); NM 19.5 pg/ml (13.8-50.7); p < 0.0001). No significant differences existed in the Copeptin, NT-proBNP, and MR-proADM concentrations between the groups. The concentration of hs-TnT was significantly higher in myocarditis when myocardial viral genome was detected (37.4 pg/ml (21.9-163.6) vs. 20 pg/ml (14-44.4); p = 0.042). During follow-up, only NT-proBNP in the highest quartile (>4,225 ng/ml) was predictive for cardiac death or heart transplantation (hazard ratio 9.2; 95% confidence interval 1.7-50; p = 0.011). CONCLUSIONS: Biopsy-proven acute and viral myocarditis is associated with elevated concentrations of hs-TnT. Elevated hs-TnT is highly suggestive of acute myocarditis, if other causes of increased myocardial necrosis markers such as myocardial infarction have been systematically excluded.

Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension.

Increased renal resistive index and urinary albumin excretion are markers of hypertensive end-organ damage and renal vasoconstriction involving increased sympathetic activity. Catheter-based sympathetic renal denervation (RD) offers a new approach to reduce renal sympathetic activity and blood pressure in resistant hypertension. The influence of RD on renal hemodynamics, renal function, and urinary albumin excretion has not been studied. One hundred consecutive patients with resistant hypertension were included in the study; 88 underwent interventional RD and 12 served as controls. Systolic, diastolic, and pulse pressure, as well renal resistive index in interlobar arteries, renal function, and urinary albumin excretion, were measured before and at 3 and 6 months of follow-up. RD reduced systolic, diastolic, and pulse pressure at 3 and 6 months by 22.7/26.6 mm Hg, 7.7/9.7 mm Hg, and 15.1/17.5 mm Hg (P for all <0.001), respectively, without significant changes in the control group. SBP reduction after 6 months correlated with SBP baseline values (r=-0.46; P<0.001). There were no renal artery stenoses, dissections, or aneurysms during 6 months of follow-up. Renal resistive index decreased from 0.691±0.01 at baseline to 0.674±0.01 and 0.670±0.01 (P=0.037/0.017) at 3- and 6-month follow-up. Mean cystatin C glomerular filtration rate and urinary albumin excretion remained unchanged after RD; however, the number of patients with microalbuminuria or macroalbuminuria decreased. RD reduced blood pressure, renal resistive index, and incidence of albuminuria without adversely affecting glomerular filtration rate or renal artery structure within 6 months and appears to be a safe and effective therapeutic approach to lower blood pressure in patients with resistant hypertension.

Blood pressure and heart rate predict outcome in patients acutely admitted with suspected myocarditis without previous heart failure.

OBJECTIVE: The study investigated the prognostic impact of blood pressure and heart rate in patients acutely admitted with suspected myocarditis without previous heart failure who underwent endomyocardial biopsy. METHODS AND RESULTS: In our prospectively planned study SBP, DBP, mean arterial blood pressure (MAP) and ECGs on admission were analyzed retrospectively in 175 patients with suspected myocarditis, who underwent endomyocardial biopsy between 1994 and 2007. Patients were followed up for a median of 53 ±â€Š41 months, corresponding to a total follow-up of 9337 patient months. The primary endpoint was the time to cardiac death or heart transplantation, which occurred in 39 patients (22%). Baseline SBP was inversely associated with primary endpoint occurrence. Per 1 mmHg increase in SBP, the hazard ratio for the primary endpoint decreased by 4.3% [hazard ratio = 0.96, confidence interval (CI) = 0.94-0.98, P < 0.001]. The increased risk at a SBP below the mean value was confirmed after adjusting for the known independent predictors immunohistological signs of inflammation in biopsy samples, New York Heart Association functional class, and lack of ß-blocker treatment (hazard ratio = 2.78, CI = 1.25-6.18, P = 0.012). In the presence of all risk predictors, hazard ratio for primary endpoint was 4.97 (CI = 2.28-10.83, P < 0.001). In a subgroup analysis of patients without ß-blocker treatment, atrial fibrillation or pacemaker, a high heart rate was also associated with poor outcome (hazard ratio = 2.92, CI = 1.02-8.29, P = 0.045). CONCLUSION: In patients with suspected myocarditis without previous chronic heart failure low SBP, DBP and MAP were predictors of poor outcome. However, in patients not treated with ß-blockers, a high heart rate was a predictor for cardiac death or heart transplantation.

Procollagen propeptides: serum markers for atrial fibrosis?

BACKGROUND: Atrial fibrosis and its spatial heterogeneity are regarded as a substrate for the perpetuation of atrial arrhythmias. During collagen synthesis and degradation, collagen propeptides and telopeptides are released into the blood. This study tested the hypothesis that serum markers of collagen turnover correlate with atrial fibrosis. METHODS: We prospectively included 28 patients in sinus rhythm undergoing cardiac surgery. Plasma concentrations of the carboxy- and amino-terminal propeptide of procollagen type-I (PICP and PINP) and type-III (PIIINP), and the C-terminal telopeptide of type-I collagen (ICTP) were determined. Interstitial fibrosis of left (n = 10) and right atrial appendages (n = 28) was analyzed histologically. RESULTS: We found a correlation between left and right atrial fibrosis (r (s) = 0.79, p < 0.01). Interestingly, the higher the interstitial collagen content, the higher was the spatial heterogeneity of fibrosis (r (s) = 0.90, p < 0.001). However, PICP, PIIINP, and ICTP were not correlated to left or right atrial collagen content, or to the spatial heterogeneity of atrial fibrosis. There was a weak and even negative correlation between the serum PINP concentration and the degree of fibrosis in both the left and the right atrium (r (s) = -0.65 (p = 0.04) and r (s) = -0.42 (p = 0.03), respectively). CONCLUSIONS: A high degree of interstitial atrial fibrosis indicates a high degree of spatial heterogeneity of interstitial collagen. Although serum PICP is known to be correlated with ventricular fibrosis, this and other serum markers of collagen turnover (PINP, PIIINP, and ICTP) do not directly reflect atrial fibrosis in patients with severe cardiac disease.

Update on myocarditis.

Myocarditis is an inflammatory disease of the heart frequently resulting from viral infections and/or post-viral immune-mediated responses. It is one of the important causes of dilated cardiomyopathy worldwide. The diagnosis is presumed on clinical presentation and noninvasive diagnostic methods such as cardiovascular magnetic resonance imaging. Endomyocardial biopsy remains the gold standard for in vivo diagnosis of myocarditis. The therapeutic and prognostic benefits of endomyocardial biopsy results have recently been demonstrated in several clinical trials. Although remarkable advances in diagnosis, understanding of pathophysiological mechanisms, and treatment of acute myocarditis were gained during the last years, no standard treatment strategies could be defined as yet, apart from standard heart failure therapy and physical rest. In severe cases, mechanical support or heart transplantation may become necessary. There is some evidence that immunosuppressive and immunomodulating therapy are effective for chronic, virus-negative inflammatory cardiomyopathy. Further investigations by controlled, randomized studies are needed to definitively determine their role in the treatment of myocarditis.

Virus serology in patients with suspected myocarditis: utility or futility?

AIMS: Serological analyses of viral infection in suspected myocarditis are still widely used, although convincing evidence for their value is lacking. We determined prospectively the diagnostic value of virus serology in comparison with endomyocardial biopsy (EMB) including viral genome detection and immunohistochemistry in patients with clinically suspected myocarditis. METHODS AND RESULTS: Virus serology and state-of-the-art evaluation of EMB were performed in 124 patients (age 40 ± 15 years) with suspected myocarditis. Endomyocardial biopsy was studied for inflammation with histological and immunohistological criteria. The viral genome was detected in the myocardium by polymerase chain reaction. Acute viral infection with enterovirus, adenovirus, parvovirus B19, cytomegalovirus, human herpesvirus, and Epstein-Barr virus was diagnosed by IgM or IgA in the initial sample or IgG seroconversion in the follow-up sample. Immunohistological signs of inflammation were present in 54 patients. The viral genome was detected in the myocardium of 58 patients (47%). In 20 patients (16%), acute viral infection was diagnosed by serology. Only in 5 out of 124 patients (4%), there was serological evidence of an infection with the same virus that was detected by EMB. Sensitivity and specificity of virus serology were 9 and 77%, respectively. The positive predictive value was 25% and the negative predictive value was 49%. The lack of correlation between serology and EMB remained also for patients with biopsy-proven myocarditis and patients with time from initial symptoms to EMB procedure of ≤1 month. CONCLUSIONS: For patients with suspected myocarditis, virus serology has no relevance for the diagnosis of myocardial infection. Endomyocardial biopsy remains the gold standard in the diagnostic of viral myocarditis.

Prognostic electrocardiographic parameters in patients with suspected myocarditis.

AIMS: The objective of this study was to investigate the prognostic value of electrocardiographic (ECG) parameters for outcome in patients acutely admitted with myocarditis without previous heart failure who underwent endomyocardial biopsy. METHODS AND RESULTS: Between 1995 and 2009, 186 consecutive patients (age: 43.4 ± 13.9 years) acutely admitted with clinically suspected myocarditis were enrolled and followed up for a mean of 55.1 ± 105.1 months. Electrocardiograms recorded before myocardial biopsy were analysed for rhythm, conduction times, signs of hypertrophy, and repolarization abnormalities. The primary endpoint was time to cardiac death or heart transplantation. The mean QRS duration was 90.3 ± 24.3 ms; 158 patients had a normal QRS duration (<120 ms) and 21 patients had a prolonged QRS duration (≥ 120 ms). During follow-up, 15.8% of patients with a normal QRS duration reached the primary endpoint compared with 42.8% of patients with a prolonged baseline QRS duration [hazard ratio (HR) 3.43; 95% confidence interval (CI) 1.78-6.01; P < 0.001]. The increased risk predicted by a prolonged QRS duration was robust after adjusting for covariates (HR 2.83; CI 1.07-7.49; P = 0.012). A QTc prolongation ≥ 440 ms (P = 0.011), an abnormal QRS axis (P = 0.012), and premature ventricular beats (P = 0.018) were significant monovariate predictors but did not prove to be independent predictors for survival in multivariate analysis. Q-waves and repolarization abnormalities were neither associated with the primary endpoint nor with immunohistological signs of inflammation. Other ECG parameters were not significantly related to outcome. CONCLUSION: A prolonged QRS duration is an independent predictor for cardiac death or heart transplantation in patients with suspected myocarditis.

Comparative evaluation of left and right ventricular endomyocardial biopsy: differences in complication rate and diagnostic performance.

BACKGROUND: Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin. METHODS AND RESULTS: In this 2-center study, 755 patients with clinically suspected myocarditis (n=481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (n=274) underwent either selective LV-EMB (n=265; 35.1%), selective RV-EMB (n=133; 17.6%), or biventricular EMB (n=357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardial effusion that occurred after biventricular EMB, the minor complication rate for LV-EMB varied between 0.64% to 2.89% and for RV-EMB, between 2.24% and 5.10%. Diagnostic EMB results were achieved significantly more often in those patients who underwent biventricular EMBs (79.3%) compared to those who underwent either selective LV-EMB or selective RV-EMB (67.3%; P<0.001). In patients with biventricular EMB, myocarditis was diagnosed in LV-EMB samples in 18.7% and in RV-EMB samples in 7.9% (P=0.002) , and it was diagnosed in both ventricles in 73.4%. There were no differences in the number of positive LV-EMB, RV-EMB, or LV- and RV-EMB findings when related to the site of cardiovascular magnetic resonance-based late gadolinium enhancement. CONCLUSIONS: Both LV-EMB and RV-EMB are safe procedures if performed by experienced interventionalists. The diagnostic yield of EMB may be optimized when samples from both ventricles are available. Preferential biopsy in regions showing late gadolinium enhancement on cardiovascular magnetic resonance does not increase the number of positive diagnoses of myocarditis.

Smoking is associated with a high prevalence of microalbuminuria in hypertensive high-risk patients: data from I-SEARCH.

BACKGROUND: Microalbuminuria (MAU) is a marker of endothelial dysfunction and a predictor of cardiovascular events. The effects of cigarette smoking on the prevalence of MAU in a high-risk population with arterial hypertension are unclear. METHODS: The International Survey Evaluating Microalbuminuria Routinely by Cardiologists in patients with Hypertension (I-SEARCH) documented the clinical profile of 20,364 patients with arterial hypertension and cardiovascular risk factors. In this population, 13,690 patients had no history of smoking, 4,057 patients were former smokers and 2,617 patients were current smokers. RESULTS: The prevalence of MAU was associated with the smoking status. Consumption of 1-20 cigarettes per day leads to an increase of 6.8% in the prevalence of MAU compared to non-smokers (P < 0.001). Smoking of >20 cigarettes per day was associated with a 12.5% higher prevalence of MAU compared to non-smokers, while former smokers had a 4.7% higher prevalence of MAU. Multivariable analysis revealed that smoking was independently associated with MAU [odds ratio (OR) smoking vs. non-smoking 1.16; 95% confidence interval (CI) 1.01-1.33; P < 0.05]. Particularly, a consumption of >20 cigarettes per day was associated with high odds for MAU (OR 1.33; CI 1.01-1.75; P < 0.05). Interestingly, independently of blood pressure, the use of an angiotensin receptor blocker and an ACE was associated with significantly reduced odds ratio for MAU in the smoking group, while there was no significant association in the non-smoking group. CONCLUSION: The prevalence of MAU in hypertensive patients is higher in smokers than in non-smokers with a strong dose dependency.