COMPArison of Multi-Point Pacing and ConvenTional Cardiac Resynchronization Therapy Through Noninvasive Hemodynamics Measurement: Short- and Long-Term Results of the COMPACT-MPP Study.

Invasive hemodynamic studies have shown improved left ventricular (LV) performances when cardiac resynchronization therapy/defibrillator is delivered through multipoint pacing (MPP). Nowadays, strategies have become available that allow studying the same hemodynamic parameters at a noninvasive level. The aim of the present study was to evaluate the clinical implication of using a patient-tailored approach for cardiac resynchronization therapy programming based on noninvasively assessed LV hemodynamics to identify the best biventricular pacing modality between standard single-site pacing (STD) and MPP for each patient. Therefore, 51 patients with heart failure (age 69 ± 9 years, 35 men, 27% ischemic etiology) implanted with cardiac resynchronization therapy/defibrillator underwent noninvasive LV function assessment through photoplethysmography before hospital discharge for addressing dP/dt and stroke volume in both pacing modalities (STD and MPP). The modality that performed better in terms of hemodynamic improvement was permanently programmed. Global longitudinal strain (GLS) was also assessed, and repeated at 3 months. Compared with intrinsic rhythm (928 ± 486 mm Hg/s), dP/dtmax showed a trend to increase in both biventricular pacing modes (1,000 ± 577 mm Hg/s in STD, 1,036 ± 530 mm Hg/s in MPP, p = NS). MPP was associated with a wider hemodynamic improvement than was STD and was the modality of choice in 34 of 51 patients (67%). GLS at predischarge did not differ between groups (-10.3 ± 3.8% vs -10.2 ± 3.5%), but significant improvement of ejection fraction at 1 month (34.4 ± 5.3%, p <0.001) and of GLS at 3 months (-12.9 ± 2.9%, p <0.005) was observed across the entire cohort. At 3 months, 77% of patients were classified as responders. Interestingly, long-term (3 years) follow-up unveiled a reduction in all-cause mortality in the MPP group compared with the STD group. In conclusion, cardiac resynchronization therapy programming guided by acute noninvasive hemodynamics favored MPP modality and caused short-term LV positive remodeling and improved long-term outcomes. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT04299360.

Inadvertent defibrillator lead placement into the left ventricle after MitraClip implantation: A case report.

RATIONALE: Inadvertent pacemaker/defibrillator lead placement into the left ventricle is an unusual cardiac device-related complication and its diagnosis is not always easy and often misunderstood. Thromboembolic events are frequently associated with this procedural complication. Percutaneous lead extraction should be performed when diagnosis is made early after device implantation while long-life oral anticoagulation is a wise option when the diagnosis is delayed and the lead is not removed. PATIENT CONCERNS: A 65-year-old man affected by dilated cardiomyopathy, previously treated with a percutaneous mitral valve repair, with 2 MitraClip devices, and later with dual chamber cardioverter/defibrillator implantation, returned in outpatient clinics 2 months after discharge for deterioration of dyspnea; transthoracic echocardiography revealed that the shock lead had been accidentally placed in the apex of the left ventricle. DIAGNOSES: The unintentional lead malposition through the iatrogenic atrial septal defect and its presence into the mitral valve orifice, together with the 2 clip devices implanted, generated an acceleration of transvalvular diastolic flow, determining a moderate stenosis of the mitral valve, as well as promoting a worsening of the degree of valvular regurgitation. INTERVENTIONS: Oral anticoagulation therapy was started and a mechanical lead extraction was percutaneously performed. A new defibrillator lead was later appropriately positioned in the apex of the right ventricle. OUTCOMES: The patient was discharged 3 days after intervention and the follow-up, performed 1 month after discharge, was uneventful. LESSONS: Complex interventional procedures and implantation of multiple devices can increase procedural troubles and the risk of mechanical complications related to pacemaker/defibrillator implantation. Careful observation of the QRS complex morphology on the electrocardiogram (ECG), during paced rhythm, and the achievement of the echocardiographic examination, in the postprocedural phase, allow an early diagnosis of lead malposition.

MicroRNA-1 downregulation increases connexin 43 displacement and induces ventricular tachyarrhythmias in rodent hypertrophic hearts.

Downregulation of the muscle-specific microRNA-1 (miR-1) mediates the induction of pathologic cardiac hypertrophy. Dysfunction of the gap junction protein connexin 43 (Cx43), an established miR-1 target, during cardiac hypertrophy leads to ventricular tachyarrhythmias (VT). However, it is still unknown whether miR-1 and Cx43 are interconnected in the pro-arrhythmic context of hypertrophy. Thus, in this study we investigated whether a reduction in the extent of cardiac hypertrophy could limit the pathological electrical remodeling of Cx43 and the onset of VT by modulating miR-1 levels. Wistar male rats underwent mechanical constriction of the ascending aorta to induce pathologic left ventricular hypertrophy (LVH) and afterwards were randomly assigned to receive 10mg/kg valsartan, VAL (LVH+VAL) delivered in the drinking water or placebo (LVH) for 12 weeks. Sham surgery was performed for control groups. Programmed ventricular stimulation reproducibly induced VT in LVH compared to LVH+VAL group. When compared to sham controls, rats from LVH group showed a significant decrease of miR-1 and an increase of Cx43 expression and its ERK1/2-dependent phosphorylation, which displaces Cx43 from the gap junction. Interestingly, VAL administration to rats with aortic banding significantly reduced cardiac hypertrophy and prevented miR-1 down-regulation and Cx43 up-regulation and phosphorylation. Gain- and loss-of-function experiments in neonatal cardiomyocytes (NCMs) in vitro confirmed that Cx43 is a direct target of miR-1. Accordingly, in vitro angiotensin II stimulation reduced miR-1 levels and increased Cx43 expression and phosphorylation compared to un-stimulated NCMs. Finally, in vivo miR-1 cardiac overexpression by an adenoviral vector intra-myocardial injection reduced Cx43 expression and phosphorylation in mice with isoproterenol-induced LVH. In conclusion, miR-1 regulates Cx43 expression and activity in hypertrophic cardiomyocytes in vitro and in vivo. Treatment of pressure overload-induced myocyte hypertrophy reduces the risk of life-threatening VT by normalizing miR-1 expression levels with the consequent stabilization of Cx43 expression and activity within the gap junction.

Midterm clinical and echocardiographic results and predictors of mitral regurgitation recurrence following restrictive annuloplasty for ischemic cardiomyopathy.

OBJECTIVE: Although mitral restrictive annuloplasty plus coronary artery bypass grafting are considered the best therapeutic strategies for ischemic cardiomyopathy with chronic mitral regurgitation, some recurrences are still reported. We evaluated predictors for late recurrence of ischemic cardiomyopathy with chronic mitral regurgitation. METHODS: Hospital outcome and serial clinical and echocardiographic (preoperative, discharge, 6 months, end of follow-up) follow-up assessments were recorded for 82 consecutive patients with ischemic cardiomyopathy with chronic mitral regurgitation having coronary artery bypass grafting + mitral restrictive annuloplasty (2 sizes ring downsizing). Recurrent ischemic cardiomyopathy with chronic mitral regurgitation was defined by grade >or= 2 at echocardiography. RESULTS: Hospital mortality was 4.9%; 17.7 +/- 1.7 (standard error) months (range 1-55) survival was 95.5% +/- 2.5%. Two-year Kaplan-Meier freedom from reintervention was 94.2% +/- 4.2%; from rerevascularization, 87.5% +/- 11.7%; from congestive heart failure, 83.8% +/- 5.7%; from ischemic cardiomyopathy with chronic mitral regurgitation grade >or= 2, 46.5% +/- 11.2%. Recurrence of ischemic cardiomyopathy with chronic mitral regurgitation gave lower 2-year Kaplan-Meier freedom from death (P = .03) and lower 2-year freedom from congestive heart failure (P = .0001), reintervention (P = .034), and tricuspid insufficiency (P = .0001). Ischemic cardiomyopathy with chronic mitral regurgitation recurrence correlated with worsened New York Heart Association class (P = .0001), left ventricular ejection fraction (P = .024), pulmonary arterial pressures (P = .0001), left ventricular end-diastolic diameter (P = .004), left ventricular end-systolic diameter (P = .014), indexed left ventricular mass (P = .008), and coaptation depth (P = .0001). Independent predictors for recurrent ischemic cardiomyopathy with chronic mitral regurgitation were previous anterior + posterior myocardial infarction (odds ratio 3.70; confidence interval 2.93-5.41; P = .001), preoperative left ventricular end-diastolic diameter >or= 70 mm (odds ratio 3.91; confidence interval 2.65-5.22; P = .001), and coaptation depth at discharge >or= 0.5 cm (odds ratio 11.9; confidence interval 5.91-21.34; P = .0001). Preoperative left ventricular end-diastolic diameter >or= 70 mm correlated with higher congestive heart failure (P = .002), recurrent ischemic cardiomyopathy with chronic mitral regurgitation (P = .0001), worsened New York Heart Association class (P = .0001), and higher diuretics (P = .0001). Coaptation depth < 0.5 cm at discharge accounted for better survival (P = .010), lower incidence of congestive heart failure (P = .0001), lower need for diuretics (P = .0001), and improved New York Heart Association class (P = .0001). CONCLUSIONS: Failure of mitral restrictive annuloplasty is responsible for follow-up mortality and congestive heart failure and correlates with absence of cardiac reverse remodeling. Prognosis of patients having mitral restrictive annuloplasty for ischemic cardiomyopathy with chronic mitral regurgitation is good, as long as a low postoperative coaptation depth is achieved. Patients with significant left ventricular dilation should be considered for different surgical strategies.

Neurohormonal and echocardiographic results after CorCap and mitral annuloplasty for dilated cardiomyopathy.

BACKGROUND: Restrictive mitral annuloplasty (RMA) can be an effective treatment for functional mitral regurgitation in congestive heart failure (CHF). Passive cardiac restraint is another surgical approach, but the midterm results are not well characterized. METHODS: Thirty patients with functional mitral regurgitation were prospectively randomized to RMA alone or cardiac restraint with the CorCap Cardiac Support Device (Acorn Cardiovascular Inc, St. Paul, MN) and RMA. Clinical, echocardiographic, New York Heart Association (NYHA) functional class, Short Form 36-Item Health Survey (SF-36) quality of life scores, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) results were analyzed. RESULTS: No hospital deaths or device-related complications occurred. The two groups had comparable morbidity (p = 0.34). Echocardiography showed a trend towards a slightly better functional improvement during follow-up in CorCap plus RMA patients (between groups, p = 0.001). Both groups showed improved results for SF-36, NYHA, and NT-pro.BNP; however, CorCap plus RMA patients had significantly better SF-36 at discharge (p = 0.003), postoperative NYHA (p = 0.05), and NT-pro.BNP (p = 0.001). Survival (p = 0.46), freedom from CHF (p = 0.23), and rehospitalization (p = 0.28) were comparable. Patients in whom CHF developed after postoperative day 1 had higher NT-pro.BNP values (p = 0.001 at all time-points). CONCLUSIONS: Adjunctive application of CorCap with RMA correlated with better NT-pro.BNP at short-term follow-up together with slightly improved echocardiographic and functional results. This deserves further evaluation at midterm and long-term follow-up. Reduction of NT-pro.BNP at follow-up may be suggested as a prognostic index.

Successful surgical treatment of chronic ischemic mitral regurgitation achieves left ventricular reverse remodeling but does not affect right ventricular function.

OBJECTIVE: To evaluate left-sided and right-sided heart echocardiographic results after restrictive mitral annuloplasty in chronic ischemic mitral regurgitation. METHODS: Left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, left ventricular indexed mass, coaptation depth, transmitral mean gradient, systolic pulmonary arterial pressure, tricuspid annular plane systolic excursion, right ventricular ejection fraction, and tricuspid insufficiency grading were evaluated preoperatively, postoperatively, at 6 months, and at the end of the follow-up period in 64 patients undergoing restrictive mitral annuloplasty and coronary artery bypass grafting. Recurrence of chronic ischemic mitral regurgitation was defined as 2+/4+ grade or greater mitral regurgitation at any time postoperatively. RESULTS: Twenty-two months of freedom from recurrent chronic ischemic mitral regurgitation was 58.2% +/- 9.8%. Recurrent chronic ischemic mitral regurgitation did not lead to reverse remodeling of left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and ventricular indexed mass (P = not significant), with increased coaptation depth, parallel to follow-up chronic ischemic mitral regurgitation worsening. Effective restrictive mitral annuloplasty induced reverse remodeling of left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and ventricular indexed mass, improved left ventricular ejection fraction, shortened coaptation depth, and improved mean gradient (P

Mid-term echocardiographic results with different rings following restrictive mitral annuloplasty for ischaemic cardiomiopathy.

BACKGROUND: Despite restrictive mitral annuloplasty (RMA) being considered effective for chronic ischaemic mitral regurgitation (CIMR), few data exist on mid-term echocardiographic results with different prosthetic rings. Therefore, comparative echocardiographic analysis has been performed. METHODS: Sixty-four consecutive coronary artery bypass graft surgery (CABG) + RMA (downsizing by two-ring sizes; median size: 26 mm) for CIMR with a follow-up of at least 6 months were prospectively followed-up with serial echocardiograms (preoperative, discharge, 6 months, follow-up ending). Hospital mortality, follow-up clinical and echocardiographic results were analysed and compared between three groups (group A: semi-rigid band, 17 patients; group B: complete symmetric semi-rigid, 22 patients; group C: complete asymmetric semi-rigid, 25 patients). RESULTS: Hospital mortality was 6.3%; 22.8 +/- 14.7 standard deviation (SD) months (range: 6-55) survival was 96.5 +/- 2.5%; freedom from re-intervention was 94.2 +/- 4.2%, from re-revascularisation 87.5 +/- 11.7%, from > or = grade-2 mitral regurgitation 58.2 +/- 9.8% and from heart failure (CHF) 71.6 +/- 10.5%. Recurrent (> or = grade-2) CIMR resulted in lower freedom-from-CHF (p = 0.0001), worsened New York Heart Association (NYHA) classification (p = 0.0001) and absence of reverse remodelling of the left ventricular end-diastolic diameter (LVEDD; p = 0.004), systolic diameter (LVESD; p = 0.014), indexed mass (LVMi; p = 0.005) and coaptation depth (p = 0.0001). Group A showed significant worse freedom from CHF (group A: 42.8 +/- 19.5% vs group B: 88.9 +/- 10.5% vs group C: 92.3 +/- 7.5%; p = 0.049) and from recurrent CIMR (17.4 +/- 13.8% vs 82.1 +/- 11.7% vs 94.1 +/- 5.7%, respectively; p = 0.0001). Complete rings decreased the hazard of recurrent CIMR (Physio = 0.141; Adams = 0.089). Higher NYHA during follow-up was found in group A (p = 0.002 for group B and p = 0.001 for group C) with a progressive reduction of trans-mitral mean gradient (p = 0.001), and a lower degree of reverse remodelling of LVEDD (p = 0.009 and p = 0.010) and coaptation depth (p = 0.040 and p = 0.002). CONCLUSIONS: Recurrent CIMR correlates with absent ventricular reverse remodelling. Despite a higher trans-mitral gradient, complete rings achieve better results in the treatment of CIMR.